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1.
Article in English | WPRIM | ID: wpr-1010993

ABSTRACT

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.


Subject(s)
Mice , Animals , Adipose Tissue, Brown , Sirtuin 1/pharmacology , Diabetes Mellitus, Type 2/metabolism , AMP-Activated Protein Kinases/metabolism , Morus/metabolism , Flavonoids/metabolism , Prospective Studies , Signal Transduction , Adipose Tissue, White , Plant Leaves , Uncoupling Protein 1/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
2.
Article in Chinese | WPRIM | ID: wpr-1008783

ABSTRACT

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1β, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.


Subject(s)
Mice , Animals , Adipose Tissue, Brown , Molecular Docking Simulation , PPAR alpha/metabolism , Adipose Tissue, White , RNA, Messenger/metabolism
3.
Int. j. morphol ; 40(5): 1219-1227, 2022. ilus, tab
Article in English | LILACS | ID: biblio-1405274

ABSTRACT

SUMMARY: Adipose tissue morphology of different fat tissue depots can be described using the number of adipocytes and cell surface of adipocytes. This study deals with characteristics and morphometric analysis of white and brown adipose tissue depots in healthy adult laboratory mice, hamsters and rats of both sexes. The number of unilocular adipocytes in white adipose tissue differs from one adipose tissue depot to another, with the largest number of adipocytes in mice and a similar number in hamsters and rats. The smallest surface area and the largest percentage of small unilocular adipocytes were found in mice. White adipose tissue in hamsters and rats was predominantly made out of a larger percentage of medium-sized adipocytes and a smaller percentage of small and medium-sized adipocytes. Uncoupling protein 1 positive multilocular adipocytes were found in classic brown adipose tissue depots with larger percentages in mice (93.20 %) and hamsters (91.30 %), while rats had a smaller percentage (78.10 %). In white and brown adipose tissue, significant differences between species and both sexes within the same species were found, indicating the influence of sexual dimorphism. The presented morphometric results could serve as a basis for further studies concerning experimental animal models of metabolic disorders and obesity.


RESUMEN: La morfología del tejido adiposo de diferentes depósitos de tejido graso se puede describir utilizando el número de adipocitos y la superficie celular de los adipocitos. Este estudio analiza las características y el análisis morfométrico de los depósitos de tejido adiposo blanco y marrón en ratones, hamsters y ratas de laboratorio, adultos sanos de ambos sexos. El número de adipocitos uniloculares en el tejido adiposo blanco difiere de un depósito de tejido adiposo a otro, con el mayor número de adipocitos en ratones y un número similar en hámsteres y ratas. La superficie más pequeña y el mayor porcentaje de adipocitos uniloculares pequeños se encontraron en ratones. El tejido adiposo blanco en hámsteres y ratas estaba compuesto predominantemente por un mayor porcentaje de adipocitos de tamaño mediano y un porcentaje menor de adipocitos de tamaño pequeño y mediano. Los adipocitos multiloculares positivos para la proteína desacopladora 1 se encontraron en depósitos de tejido adiposo marrón clásico con mayores porcentajes en ratones (93,20 %) y hámsters (91,30 %), mientras que las ratas tenían un porcentaje menor (78,10 %). En el tejido adiposo blanco y pardo se encontraron diferencias significativas entre especies y entre ambos sexos dentro de una misma especie, lo que indica la influencia del dimorfismo sexual. Los resultados morfométricos presentados podrían servir como base para futuros estudios sobre modelos animales experimentales de trastornos metabólicos y obesidad.


Subject(s)
Animals , Male , Female , Mice , Rats , Adipose Tissue, Brown/anatomy & histology , Subcutaneous Fat/anatomy & histology , Adipose Tissue, White/anatomy & histology , Viscera/anatomy & histology , Cricetinae , Sex Characteristics , Models, Animal
4.
Arch. endocrinol. metab. (Online) ; 64(4): 479-482, July-Aug. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131118

ABSTRACT

ABSTRACT Objective Fibroblast growth factor 21 (FGF21) is among the activators that can stimulate thermogenesis in the white adipose tissue and brown adipose tissue. People with obesity have elevated blood levels of FGF21, but also develop resistance to its action, impairing its beneficial role. Inversely, clinical treatments to weight loss has been pointed out as an important therapy for increasing and recovering sensitivity to FGF21. The aim was to analyse the effect of long-term weight loss interdisciplinary intervention on FGF21 and body composition. Subjects and methods Eighty-six post-pubertal obese adolescents (14-19 years-old), were submitted to 20 weeks of weight loss therapy (clinical, nutritional, psychological and physical exercise support). Anthropometric measures, body composition and rest metabolic rate (RMR) by bioelectrical impedance, and serum FGF21 sample by ELISA were evaluated. The adolescents were grouped according to FGF21 individual delta variations after therapy: Higher Increase (HI); lower increase (LI); lower decrease (LD); higher decrease (HD). Results All groups present weight loss. Only in FGF21 ≥ 76,5 pg/mL variation the free-fat-mass and rest metabolic rate were preserved and to others group these variables were significantly reduced. Conclusion High increase in FGF21 can contribute to preservation of FFM and RMR after weight loss therapy, could have important implications for energy balance regulation. Future studies are necessary to continue determining the role of magnitude effects of FGF21 levels in obesity to improve clinical practice, especially in paediatrics population.


Subject(s)
Humans , Adolescent , Weight Loss , Fibroblast Growth Factors/blood , Obesity , Energy Metabolism , Adipose Tissue, White
5.
Gac. méd. Méx ; 156(2): 143-150, mar.-abr. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1249885

ABSTRACT

Resumen El tejido adiposo es un órgano endocrino con gran actividad metabólica. A la fecha se han descubierto innumerables adipocinas y lipocinas, péptidos y lípidos con actividad biológica, secretadas por el tejido adiposo. Se sabe que tanto el tejido adiposo blanco como el pardo y el beige contribuyen a la homeostasis energética y a la regulación metabólica. Esta revisión tiene como finalidad comunicar los hallazgos más recientes relativos al tejido adiposo según su color y la relación de este con las alteraciones metabólicas asociadas a la obesidad. Después de la revisión de la literatura especializada, se identificó que en una misma estructura pueden coexistir poblaciones blancas, pardas y beige, que modifican el estado metabólico global en situaciones fisiológicas o patológicas.


Abstract Adipose tissue is an endocrine organ with high metabolic activity. Countless adipose tissue-secreted adipokines and lipokines, as well as peptides and lipids with biological activity have thus far been discovered. Both white and brown and beige adipose tissue are known to contribute to energy homeostasis and metabolic regulation. The purpose of this review is to report on the most recent findings related to adipose tissue according to its color and its relationship with metabolic alterations associated with obesity. After a review of the specialized literature, white, brown and beige adipocyte populations were identified to be able to coexist within the same structure, and to modify global metabolic state in physiological or pathological situations.


Subject(s)
Adipose Tissue, Brown , Adipose Tissue, White , Adipose Tissue, Beige , Color
7.
Einstein (Säo Paulo) ; 18: eAO4784, 2020. tab, graf
Article in English | LILACS | ID: biblio-1039736

ABSTRACT

ABSTRACT Objective To evaluate the effect of three types of muscular resistance training on adiposity, inflammation levels and insulin activity in Swiss mice with fat-rich diet-induced obesity. Methods Lean and obese male Swiss mice were selected and allocated to one of eight groups comprising eight mice each, as follows: standard diet + no training; standard diet + muscular resistance training; standard diet + hypertrophy training; standard diet + strength training; high-fat diet + no training; high-fat diet + muscular resistance training; high-fat diet + hypertrophy training; high-fat diet + strength training. The training protocol consisted of stair climbing for a 10-week period. Blood samples were collected for lactate analysis, glucose level measurement and insulin tolerance test. After euthanasia, adipose tissues were removed and weighed for adiposity index determination. Fragments of epididymal adipose tissue were then embedded for histological analysis or homogenized for tumor necrosis factor alpha level determination using the ELISA method. Results Ausency of differences in total training volume and blood lactate levels overall emphasize the similarity between the different resistance training protocols. Body weight loss, reduced adipocyte area and lower adiposity index were observed in trained obese mice, regardless of training modality. Different training protocols also improved insulin sensitivity and reduced inflammation levels. Conclusion Resistance training protocols were equally effective in reducing body fat, inflammation levels and insulin resistance in obese mice.


RESUMO Objetivo Avaliar os efeitos de três tipos de treinamentos de resistência na adiposidade, na inflamação e na ação da insulina em camundongos Swiss obesos por dieta hiperlipídica. Métodos Camundongos Swiss machos magros e obesos foram selecionados e posteriormente separados em oito grupos com oito animais em cada: dieta padrão + não treinado; dieta padrão + treinamento de resistência muscular; dieta padrão + treinamento de hipertrofia; dieta padrão + treinamento de força; dieta hiperlipídica + não treinado; dieta hiperlipídica + treinamento de resistência muscular; dieta hiperlipídica + treinamento de hipertrofia; e dieta hiperlipídica + treinamento de força. O protocolo de treinamento consistiu em escaladas, por um período de 10 semanas. Amostras de sangue foram coletadas para análises de lactato, glicemia e teste de tolerância à insulina. Após eutanásia, os tecidos adiposos foram retirados e pesados para determinar o índice de adiposidade. Em seguida, parte do tecido adiposo epididimal foi emblocado para análises histológicas, e outra parte foi homogeneizada para análises de fator de necrose tumoral alfa por ELISA. Resultados O volume total de treinamento e a concentração sanguínea de lactato não diferiram entre os três treinos resistidos, sugerindo similaridade entre eles. Nos animais obesos, as três modalidades de treinamento reduziram o peso corporal, a área adipocitária e o índice de adiposidade. Os três tipos de treinamentos ainda melhoraram a tolerância à insulina e reduziram a inflamação. Conclusão Os protocolos de treinamento resistido foram igualmente efetivos em reduzir a adiposidade, a inflamação e a resistência à ação da insulina em camundongos obesos.


Subject(s)
Animals , Male , Mice , Physical Conditioning, Animal/physiology , Insulin Resistance/physiology , Adiposity/physiology , Muscle Stretching Exercises/methods , Hypertrophy/physiopathology , Inflammation/physiopathology , Obesity/physiopathology , Time Factors , Blood Glucose/analysis , Body Weight/physiology , Enzyme-Linked Immunosorbent Assay , Reproducibility of Results , Tumor Necrosis Factor-alpha/analysis , Adipose Tissue, White/physiopathology , Resistance Training/methods , Diet, High-Fat , Mice , Mice, Obese
8.
Int. braz. j. urol ; 45(6): 1136-1143, Nov.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1056335

ABSTRACT

ABSTRACT Purpose: To prospectively evaluate the association of adherent perinephric fat (APF) on perioperative outcomes of robotic-assisted partial nephrectomy (RAPN) following elimination of the surgical learning curve. Materials and Methods: 305 consecutive RAPNs performed by a single experienced surgeon were analyzed. The first 100 RAPNs were considered the learning curve and therefore excluded. APF was defined as the necessity of subcapsular renal dissection to mobilize the tumor from surrounding perinephric fat. Perioperative outcomes were evaluated including operative time, warm ischemia time (WIT), postoperative complications, length of stay, margins, ischemia, and complications score (MIC), estimated blood loss (EBL), and change in pre-operative to postoperative day 1 (POD 1) laboratory values. After correction for multiple comparisons, P values ≤0.0045 were considered statistically significant but associations with P values ≤0.05 were also mentioned in the study results. Results: Fifty-eight (28.3%) patients had APF. Patients with APF had longer operative times compared to those without APF (median, 213 vs. 192 minutes, P <0.001). There was some evidence of higher increase in change in creatinine from preoperative to POD 1 among those with APF compared to those without APF, although this was not statistically significant (median, 0.2 vs. 0.1mg/dL, P=0.03). There were no other statistically significant associations between presence of APF and perioperative outcomes. Conclusions: APF is associated with increased operative time but no change in other perioperative outcomes. Surgeon experience does not affect perioperative outcomes associated with APF.


Subject(s)
Humans , Male , Female , Adult , Aged , Aged, 80 and over , Young Adult , Clinical Competence , Adipose Tissue, White/surgery , Learning Curve , Robotic Surgical Procedures/methods , Nephrectomy/methods , Postoperative Complications , Body Mass Index , Prospective Studies , Treatment Outcome , Statistics, Nonparametric , Perioperative Period , Operative Time , Robotic Surgical Procedures/adverse effects , Glomerular Filtration Rate , Middle Aged , Nephrectomy/adverse effects
9.
Article in English | WPRIM | ID: wpr-741699

ABSTRACT

BACKGROUND/OBJECTIVES: Fasting and postprandial hyperglycemia should be controlled to avoid complications of diabetes mellitus. This study investigated the effects of autumn olive (Elaeagnus umbellata Thunb.) berry (AOB) on fasting and postprandial hyperglycemia in mice. MATERIALS/METHODS: In vitro α-glucosidase inhibitory effect of AOB was determined. Maltose solution (2 g/kg) with and without AOB extract at 500 mg/kg or acarbose at 50 mg/kg was orally administered to normal mice after overnight fasting and glucose levels were measured. To study the effects of chronic consumption of AOB, db/db mice received the basal diet or a diet containing AOB extract at 0.4% or 0.8%, or acarbose at 0.04% for 7 weeks. Blood glycated hemoglobin and serum glucose and insulin levels were measured. Expression of adiponectin protein in epididymal white adipose tissue was determined by Western blotting. RESULTS: In vitro inhibitory effect of AOB extract on α-glucosidase was 92% as strong as that of acarbose. The AOB extract (500 mg/kg) or acarbose (50 mg/kg) significantly suppressed the postprandial rise of blood glucose after maltose challenge and the area under the glycemic response curve in normal mice. The AOB extract at 0.4% or 0.8% of diet or acarbose at 0.04% of diet significantly lowered levels of serum glucose and blood glycated hemoglobin and homeostasis model assessment for insulin resistance values in db/db mice. The expression of adiponectin protein in adipose tissue was significantly elevated by the consumption of AOB at 0.8% of diet. CONCLUSIONS: Autumn olive (E. umbellata Thunb.) berry may reduce postprandial hyperglycemia by inhibiting α-glucosidase in normal mice. Chronic consumption of AOB may alleviate fasting hyperglycemia in db/db mice partly by inhibiting α-glucosidase and upregulating adiponectin expression.


Subject(s)
Animals , Mice , Acarbose , Adiponectin , Adipose Tissue , Adipose Tissue, White , Blood Glucose , Blotting, Western , Diabetes Complications , Diabetes Mellitus , Diet , Fasting , Fruit , Glucose , Glycated Hemoglobin , Homeostasis , Hyperglycemia , In Vitro Techniques , Insulin , Insulin Resistance , Maltose , Olea
10.
Article in English | WPRIM | ID: wpr-785715

ABSTRACT

Chronic energy surplus increases body fat, leading to obesity. Since obesity is closely associated with most metabolic complications, pathophysiological roles of adipose tissue in obesity have been intensively studied. White adipose tissue is largely divided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). These two white adipose tissues are similar in their appearance and lipid storage functions. Nonetheless, emerging evidence has suggested that SAT and VAT have different characteristics and functional roles in metabolic regulation. It is likely that there are intrinsic differences between VAT and SAT. In diet-induced obese animal models, it has been reported that adipogenic progenitors in VAT rapidly proliferate and differentiate into adipocytes. In obesity, VAT exhibits elevated inflammatory responses, which are less prevalent in SAT. On the other hand, SAT has metabolically beneficial effects. In this review, we introduce recent studies that focus on cellular and molecular components modulating adipogenesis and immune responses in SAT and VAT. Given that these two fat depots show different functions and characteristics depending on the nutritional status, it is feasible to postulate that SAT and VAT have different developmental origins with distinct adipogenic progenitors, which would be a key determining factor for the response and accommodation to metabolic input for energy homeostasis.


Subject(s)
Adipocytes , Adipogenesis , Adipose Tissue , Adipose Tissue, White , Energy Metabolism , Hand , Homeostasis , Inflammation , Intra-Abdominal Fat , Models, Animal , Nutritional Status , Obesity , Stem Cells , Subcutaneous Fat
11.
Article in Chinese | WPRIM | ID: wpr-776556

ABSTRACT

OBJECTIVE@#To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning.@*METHODS@#The male C57BL/6J mice were divided into three groups: normal control group, genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days, normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region, inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1 (UCP1) was determined by real-time PCR and Western blot respectively.@*RESULTS@#The wet weight of white fat in genipin-treated mice was decreased by 16% , and 28% in that of cold-stimulus mice, compared with the normal control group (P<0.05).After treatments of genipin and cold-stimulus, the color of white adipose tissues was darker, and the size of lipid droplets in adipocytes was smaller, whereas the number was increased.Compared with the normal control group, UCP1 expression was increased obviously in fat tissues, including the subcutaneous and visceral white adipose tissues, and brown adipose tissue after treated with genipin and cold-stimulus (P<0.05).@*CONCLUSION@#Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression, which could contribute to the loss of body weight against obesity.


Subject(s)
Animals , Male , Mice , Adipose Tissue, Brown , Adipose Tissue, White , Cholagogues and Choleretics , Pharmacology , Iridoids , Pharmacology , Mice, Inbred C57BL , Obesity , Drug Therapy , Uncoupling Protein 1 , Up-Regulation
12.
Article in English | WPRIM | ID: wpr-773368

ABSTRACT

OBJECTIVE@#We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats.@*METHODS@#In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw).@*RESULTS@#In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity.@*CONCLUSION@#These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.


Subject(s)
Animals , Male , Mice , Rats , 3T3 Cells , Adipocytes , Physiology , Adipose Tissue, Brown , Physiology , Adipose Tissue, White , Physiology , Animal Feed , Anti-Obesity Agents , Metabolism , Cell Differentiation , Diet , Fermentation , Hordeum , Chemistry , Lactobacillus plantarum , Chemistry , Obesity , Drug Therapy , Genetics , Plant Extracts , Chemistry , Probiotics , Metabolism , Random Allocation , Rats, Sprague-Dawley , Uncoupling Protein 1 , Genetics , Metabolism
13.
Article in English | WPRIM | ID: wpr-719634

ABSTRACT

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.


Subject(s)
Animals , Mice , Activating Transcription Factor 3 , Adipocytes , Adiponectin , Adipose Tissue, White , Diet , Insulin Resistance , Metabolic Diseases , Mice, Obese , Microarray Analysis , Obesity , RNA, Messenger
14.
Article in Chinese | WPRIM | ID: wpr-781246

ABSTRACT

OBJECTIVE@#To investigate the time-sequential expression of a novel long non-coding RNA, lnc AK079912, in metabolically related tissues and during adipose tissue development and browning in mice.@*METHODS@#The interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue (sWAT), epididymal white adipose tissue (eWAT), liver tissues and muscular tissues were collected from 8-week-old C57BL/6J mice. The iBAT, sWAT and eWAT were also collected from the mice during development (0 day, 21 days, 8 weeks and 6 months after birth) and from 8- to 10-week- mice with cold exposure (4 ℃) and intraperitoneal injections of CL316, 243 (1 μg/g body weight) for 1 to 5 days. Trizol was used to extract the total RNA from the tissues, and RT-qPCR was performed to detect the expressions of lnc AK079912. Isolated mouse preadipocytes in primary culture were induced for adipogenic differentiation for 9 days and then treated with CL316, 243 (2 μmol/L) for different durations (no longer than 24 h); the expression of lnc AK079912 in the cells was detected using RT-qPCR at different time points of the treatment.@*RESULTS@#Lnc AK079912 was highly expressed in mouse adipose tissues, the highest in iBAT, followed by the muscular tissue, but was hardly detected in the liver tissue. The expression level of lnc AK079912 increased progressively in iBAT and sWAT during development of the mice, while its expression in eWAT showed an initial increase followed by a reduction at 8 weeks ( 0.05). The expression of lnc AK079912 was significantly decreased in iBAT and eWAT ( < 0.05) but increased in eWAT from mice with intraperitoneal injection of CL316, 243 for 1 to 5 days ( < 0.05). The expression level in the adipocytes in primary culture was significantly increased in response to treatment with CL316, 243 ( < 0.05).@*CONCLUSIONS@#Lnc AK079912 is highly expressed in mouse adipose tissue, and its expression gradually increases with the development of adipose tissue but with a depot-specific difference. Lnc AK079912 is significantly elevated in the early stage of adipose tissue browning, indicating its important role in the development and browning of adipose tissue.


Subject(s)
Animals , Male , Mice , Adipocytes , Adipogenesis , Adipose Tissue, Brown , Adipose Tissue, White , Mice, Inbred C57BL , RNA, Long Noncoding
15.
Article in Chinese | WPRIM | ID: wpr-813044

ABSTRACT

To characterize the timeliness of β3 adrenergic receptor agonist CL316,243-induced browning of white adipose tissues in mice.
 Methods: Male C57BL/6J mice at 10 weeks of age were housed in conventional cages and given sterile saline for the control group or CL316,243 (1 μg/g) for the experimental group via intraperitoneal injection for 1, 3, and 5 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous white adipose (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological and gene expression analysis.
 Results: Compared with the control group, intraperitoneal injection of CL316,243 reduced the weight of eWAT on the first day. Meanwhile, CL316,243 continuously promoted the mRNA and protein expression of uncoupling protein-1 (UCP-1) in sWAT and eWAT. Furthermore, CL316,243 injection significantly decreased the food intake and weight gain of the mice, and reduced the diameter of adipocyte and accumulation of small lipid droplets in adipose tissues.
 Conclusion: CL316,243 can induce the brown-like remodeling in adipose tissues of mice in vivo, which show different time-dependent manners in different adipose tissues.


Subject(s)
Animals , Male , Mice , Adipose Tissue, Brown , Adipose Tissue, White , Adrenergic beta-Agonists , Mice, Inbred C57BL , Uncoupling Protein 1
16.
Protein & Cell ; (12): 152-163, 2018.
Article in English | WPRIM | ID: wpr-756957

ABSTRACT

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.


Subject(s)
Animals , Humans , Adipocytes, Beige , Cell Biology , Adipose Tissue, Brown , Cell Biology , Metabolism , Adipose Tissue, White , Cell Biology , Aging , Metabolism
17.
Article in English | WPRIM | ID: wpr-740091

ABSTRACT

BACKGROUND: Oxidative stress occurs in white adipose tissue and dysregulates the expression of adipokines secreted from adipocytes. Since adipokines influence inflammation, supplementation with antioxidants might be beneficial for preventing oxidative stress-mediated inflammation in adipocytes and inflammation-associated complications. β-Carotene is the most prominent antioxidant carotenoid and scavenges reactive oxygen species in various tissues. The purpose of this study was to determine whether β-carotene regulates the expression of adipokines, such as adiponectin, monocyte chemoattractant protein-1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES) in 3T3-L1 adipocytes treated with glucose/glucose oxidase (G/GO). METHODS: 3T3-L1 adipocytes were cultured with or without β-carotene and treated with G/GO, which produces H2O2. mRNA and protein levels in the medium were determined by a real-time PCR and an ELISA. DNA binding activities of transcription factors were assessed using an electrophoretic mobility shift assay. RESULTS: G/GO treatment increased DNA binding affinities of redox-sensitive transcription factors, such as NF-κB, activator protein-1 (AP-1), and STAT3. G/GO treatment reduced the expression of adiponectin and increased the expression of MCP-1 and RANTES. G/GO-induced activations of NF-κB, AP-1, and STAT3 were inhibited by β-carotene. G/GO-induced dysregulation of adiponectin, MCP-1, and RANTES were significantly recovered by treatment with β-carotene. CONCLUSIONS: β-Carotene inhibits oxidative stress-induced inflammation by suppressing pro-inflammatory adipokines MCP-1 and RANTES, and by enhancing adiponectin in adipocytes. β-Carotene may be beneficial for preventing oxidative stress-mediated inflammation, which is related to adipokine dysfunction.


Subject(s)
Adipocytes , Adipokines , Adiponectin , Adipose Tissue, White , Antioxidants , beta Carotene , Chemokine CCL2 , Chemokine CCL5 , DNA , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Inflammation , Oxidative Stress , Oxidoreductases , Reactive Oxygen Species , Real-Time Polymerase Chain Reaction , RNA, Messenger , Transcription Factor AP-1 , Transcription Factors
18.
Article in English | WPRIM | ID: wpr-714209

ABSTRACT

Present study investigated the morphologic changes of autonomic nerves in the adipose tissue in diabetic animal model. Male obese type 2 diabetic db/db mice and age matched non-diabetic db/m control mice were used. Epididymal adipose tissue from diabetic db/db mice with that from control heterozygous db/m mice was compared using confocal microscopy-based method to visualize intact whole adipose tissue. Immunohistochemistry with tyrosine hydroxylase for sympathetic (SP), choline acetyltransferase for parasympathetic (PSP), and protein gene product 9.5 (PGP 9.5) for whole autonomic nerves was performed. The quantity of immunostained portion of SP, PSP, and PGP 9.5 stained nerve fibers showed decreased trend in diabetic group; however, the ratio of SP/PSP of adipose tissue was higher in diabetic group compared with control group as follows (0.70±0.30 vs. 0.95±0.25, P < 0.05; normal vs. diabetic, respectively). Both SP and PSP nerve fibers were observed in white adipose tissue and PSP nerve fibers were suggested as more decreased in diabetes based on our observation.


Subject(s)
Animals , Humans , Male , Mice , Adipocytes , Adipose Tissue , Adipose Tissue, White , Autonomic Pathways , Choline O-Acetyltransferase , Diabetes Mellitus , Immunohistochemistry , Methods , Models, Animal , Nerve Fibers , Peripheral Nerves , Tyrosine 3-Monooxygenase
19.
An. acad. bras. ciênc ; 89(4): 2887-2900, Oct.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-886872

ABSTRACT

ABSTRACT Here, we evaluated whether the exposure of rats to a cafeteria diet pre- and/or post-weaning, alters histological characteristics in the White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and liver of adult male offspring. Female Wistar rats were divided into Control (CTL; fed on standard rodent chow) and Cafeteria (CAF; fed with the cafeteria diet throughout life, including pregnancy and lactation). After birth, only male offspring (F1) were maintained and received the CTL or CAF diets; originating four experimental groups: CTL-CTLF1; CTL-CAFF1; CAF-CTLF1; CAF-CAFF1. Data of biometrics, metabolic parameters, liver, BAT and WAT histology were assessed and integrated using the Principal Component Analysis (PCA). According to PCA analysis worse metabolic and biometric characteristics in adulthood are associated with the post-weaning CAF diet compared to pre and post weaning CAF diet. Thus, the CTL-CAFF1 group showed obesity, higher deposition of fat in the liver and BAT and high fasting plasma levels of glucose, triglycerides and cholesterol. Interestingly, the association between pre and post-weaning CAF diet attenuated the obesity and improved the plasma levels of glucose and triglycerides compared to CTL-CAFF1 without avoiding the higher lipid accumulation in BAT and in liver, suggesting that the impact of maternal CAF diet is tissue-specific.


Subject(s)
Animals , Male , Female , Pregnancy , Rats , Adipose Tissue, Brown/pathology , Dietary Fats/adverse effects , Diet , Adipose Tissue, White/pathology , Lipids/blood , Liver/pathology , Prenatal Exposure Delayed Effects , Weaning , Energy Intake , Rats, Wistar
20.
Einstein (Säo Paulo) ; 15(4): 507-511, Oct.-Dec. 2017. graf
Article in English | LILACS | ID: biblio-891425

ABSTRACT

ABSTRACT Obesity is characterized by an excessive increase in the adipose tissue mass, and is associated with higher incidence of several chronic metabolic diseases, such as type 2 diabetes. Therefore, its increasing prevalence is a public health concern, and it is important to better understand its etiology to develop new therapeutic strategies. Evidence accumulated over the years indicates that obesity is associated with a marked activation in adipose tissue of the mechanistic target of rapamycin complex 1 (mTORC1), a signaling pathway that controls lipid metabolism, and adipocyte formation and maintenance. Curiously, mTORC1 is also involved in the control of nonshivering thermogenesis and recruitment as well as browning of white adipose tissue. In this review, we explored mTORC1 functions in adipocytes and presented evidence, suggesting that mTORC1 may either increase or reduce adiposity, depending on the conditions and activation levels.


RESUMO A obesidade é caracterizada pelo aumento excessivo da massa de tecido adiposo, estando associada à maior incidência de diversas doenças metabólicas crônicas, como diabetes tipo 2. Sua crescente prevalência é uma questão de saúde pública, e faz-se importante compreender melhor sua etiologia, para desenvolver novas estratégias terapêuticas. As evidências acumuladas por muitos anos indicam que a obesidade está associada à significativa ativação no tecido adiposo do complexo 1 da proteína alvo mecanístico da rapamicina (mTORC1), uma via de sinalização que regula o metabolismo de lipídeos, bem como a formação e manutenção de adipócitos. Curiosamente, mTORC1 também está envolvido no controle da termogênese, independente do tremor muscular, e no recrutamento e browning de tecido adiposo branco. Nesta revisão, exploramos as diferentes funções do mTORC1 em adipócitos e apresentamos evidências que sugerem que o mTORC1 pode aumentar ou reduzir a adiposidade, dependendo das condições e de seu nível de ativação.


Subject(s)
Humans , Animals , Adiposity/physiology , Mechanistic Target of Rapamycin Complex 1/physiology , Obesity/metabolism , Adipose Tissue, Brown/metabolism , Adipocytes/metabolism , Thermogenesis/physiology , Diabetes Mellitus, Type 2/metabolism , Lipid Metabolism/physiology , Adipose Tissue, White/metabolism
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