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1.
Int J Mol Sci ; 23(19)2022 Oct 07.
Article in English | MEDLINE | ID: covidwho-2066142

ABSTRACT

The role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of energy homeostasis remains poorly understood. In this study, we used a transgenic fat-1 mouse model, which can produce n-3 PUFAs endogenously, to investigate how n-3 PUFAs regulate the morphology and function of brown adipose tissue (BAT). We found that high-fat diet (HFD) induced a remarkable morphological change in BAT, characterized by "whitening" due to large lipid droplet accumulation within BAT cells, associated with obesity in wild-type (WT) mice, whereas the changes in body fat mass and BAT morphology were significantly alleviated in fat-1 mice. The expression of thermogenic markers and lypolytic enzymes was significantly higher in fat-1 mice than that in WT mice fed with HFD. In addition, fat-1 mice had significantly lower levels of inflammatory markers in BAT and lipopolysaccharide (LPS) in plasma compared with WT mice. Furthermore, fat-1 mice were resistant to LPS-induced suppression of UCP1 and PGC-1 expression and lipid deposits in BAT. Our data has demonstrated that high-fat diet-induced obesity is associated with impairments of BAT morphology (whitening) and function, which can be ameliorated by elevated tissue status of n-3 PUFAs, possibly through suppressing the effects of LPS on inflammation and thermogenesis.


Subject(s)
Adipose Tissue, Brown , Fatty Acids, Omega-3 , Adipose Tissue, Brown/metabolism , Animals , Diet, High-Fat/adverse effects , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Unsaturated/metabolism , Lipopolysaccharides/pharmacology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Obesity/genetics , Obesity/metabolism , Thermogenesis
2.
Int J Mol Sci ; 23(13)2022 Jul 05.
Article in English | MEDLINE | ID: covidwho-1934138

ABSTRACT

Long-chain noncoding RNAs (lncRNAs) are RNAs that do not code for proteins, widely present in eukaryotes. They regulate gene expression at multiple levels through different mechanisms at epigenetic, transcription, translation, and the maturation of mRNA transcripts or regulation of the chromatin structure, and compete with microRNAs for binding to endogenous RNA. Adipose tissue is a large and endocrine-rich functional tissue in mammals. Excessive accumulation of white adipose tissue in mammals can cause metabolic diseases. However, unlike white fat, brown and beige fats release energy as heat. In recent years, many lncRNAs associated with adipogenesis have been reported. The molecular mechanisms of how lncRNAs regulate adipogenesis are continually investigated. In this review, we discuss the classification of lncRNAs according to their transcriptional location. lncRNAs that participate in the adipogenesis of white or brown fats are also discussed. The function of lncRNAs as decoy molecules and RNA double-stranded complexes, among other functions, is also discussed.


Subject(s)
Adipogenesis , RNA, Long Noncoding , Adipocytes/metabolism , Adipocytes, Brown/metabolism , Adipogenesis/genetics , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Animals , Mammals/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
3.
Cells ; 11(13)2022 07 04.
Article in English | MEDLINE | ID: covidwho-1917305

ABSTRACT

In the last 30 years the adipose cell has been object of several studies, turning its reputation from an inert cell into the main character involved in the pathophysiology of multiple diseases, including the ongoing COVID-19 pandemic, which has changed the clinical scenario of the last two years. Composed by two types of tissue (white and brown), with opposite roles, the adipose organ is now classified as a real endocrine organ whose dysfunction is involved in different diseases, mainly obesity and type 2 diabetes. In this mini-review we aim to retrace the adipose organ history from physiology to physiopathology, to provide therapeutic perspectives for the prevention and treatment of its two main related diseases (obesity and type 2 diabetes) and to summarize the most recent discoveries linking adipose tissue to COVID-19.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Adipose Tissue, Brown/metabolism , Diabetes Mellitus, Type 2/metabolism , Humans , Obesity/metabolism , Pandemics
4.
Int J Mol Sci ; 23(9)2022 Apr 28.
Article in English | MEDLINE | ID: covidwho-1847341

ABSTRACT

Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is traditionally used to image human BAT activity. However, the primary energy source of BAT is derived from intracellular fatty acids and not glucose. Beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) is a fatty acid analogue amenable to in vivo imaging by single photon emission computed tomography/CT (SPECT/CT) when radiolabeled with iodine isotopes. In this study, we compare the use of 18FDG-PET/CT and 125I-BMIPP-SPECT/CT for fat imaging to ascertain whether BMIPP is a more robust candidate for the non-invasive evaluation of metabolically active adipose depots. Interscapular BAT, inguinal white adipose tissue (iWAT), and gonadal white adipose tissue (gWAT) uptake of 18FDG and 125I-BMIPP was quantified in mice following treatment with the BAT-stimulating drug CL-316,243 or saline vehicle control. After CL-316,243 treatment, uptake of both radiotracers increased in BAT and iWAT. The standard uptake value (SUVmean) for 18FDG and 125I-BMIPP significantly correlated in these depots, although uptake of 125I-BMIPP in BAT and iWAT more closely mimicked the fold-change in metabolic rate as measured by an extracellular flux analyzer. Herein, we find that imaging BAT with the radioiodinated fatty acid analogue BMIPP yields more physiologically relevant data than 18FDG-PET/CT, and its conventional use may be a pivotal tool for evaluating BAT in both mice and humans.


Subject(s)
Adipose Tissue, Brown , Fluorodeoxyglucose F18 , Adipose Tissue, Brown/diagnostic imaging , Adipose Tissue, Brown/metabolism , Animals , Fatty Acids/metabolism , Fluorodeoxyglucose F18/metabolism , Iodobenzenes , Mice , Obesity/metabolism , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Radiopharmaceuticals/metabolism , Tomography, Emission-Computed, Single-Photon/methods
5.
Int J Mol Sci ; 22(16)2021 Aug 07.
Article in English | MEDLINE | ID: covidwho-1662667

ABSTRACT

Glucocorticoids (GCs) are hormones that aid the body under stress by regulating glucose and free fatty acids. GCs maintain energy homeostasis in multiple tissues, including those in the liver and skeletal muscle, white adipose tissue (WAT), and brown adipose tissue (BAT). WAT stores energy as triglycerides, while BAT uses fatty acids for heat generation. The multiple genomic and non-genomic pathways in GC signaling vary with exposure duration, location (adipose tissue depot), and species. Genomic effects occur directly through the cytosolic GC receptor (GR), regulating the expression of proteins related to lipid metabolism, such as ATGL and HSL. Non-genomic effects act through mechanisms often independent of the cytosolic GR and happen shortly after GC exposure. Studying the effects of GCs on adipose tissue breakdown and generation (lipolysis and adipogenesis) leads to insights for treatment of adipose-related diseases, such as obesity, coronary disease, and cancer, but has led to controversy among researchers, largely due to the complexity of the process. This paper reviews the recent literature on the genomic and non-genomic effects of GCs on WAT and BAT lipolysis and proposes research to address the many gaps in knowledge related to GC activity and its effects on disease.


Subject(s)
Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Genomics , Glucocorticoids , Lipogenesis , Lipolysis , Animals , Glucocorticoids/genetics , Glucocorticoids/metabolism , Humans
6.
Cells ; 10(12)2021 12 08.
Article in English | MEDLINE | ID: covidwho-1597185

ABSTRACT

Beta-3 adrenergic receptor activation via exercise or CL316,243 (CL) induces white adipose tissue (WAT) browning, improves glucose tolerance, and reduces visceral adiposity. Our aim was to determine if sex or adipose tissue depot differences exist in response to CL. Daily CL injections were administered to diet-induced obese male and female mice for two weeks, creating four groups: male control, male CL, female control, and female CL. These groups were compared to determine the main and interaction effects of sex (S), CL treatment (T), and WAT depot (D). Glucose tolerance, body composition, and energy intake and expenditure were assessed, along with perigonadal (PGAT) and subcutaneous (SQAT) WAT gene and protein expression. CL consistently improved glucose tolerance and body composition. Female PGAT had greater protein expression of the mitochondrial uncoupling protein 1 (UCP1), while SQAT (S, p < 0.001) was more responsive to CL in increasing UCP1 (S×T, p = 0.011) and the mitochondrial biogenesis induction protein, PPARγ coactivator 1α (PGC1α) (S×T, p = 0.026). Females also displayed greater mitochondrial OXPHOS (S, p < 0.05) and adiponectin protein content (S, p < 0.05). On the other hand, male SQAT was more responsive to CL in increasing protein levels of PGC1α (S×T, p = 0.046) and adiponectin (S, p < 0.05). In both depots and in both sexes, CL significantly increased estrogen receptor beta (ERß) and glucose-related protein 75 (GRP75) protein content (T, p < 0.05). Thus, CL improves systemic and adipose tissue-specific metabolism in both sexes; however, sex differences exist in the WAT-specific effects of CL. Furthermore, across sexes and depots, CL affects estrogen signaling by upregulating ERß.


Subject(s)
Adipose Tissue, Brown/metabolism , HSP70 Heat-Shock Proteins/genetics , Membrane Proteins/genetics , PPAR gamma/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Uncoupling Protein 1/genetics , Adipose Tissue/metabolism , Adipose Tissue, Brown/growth & development , Adipose Tissue, White/metabolism , Animals , Body Composition/genetics , Dioxoles/pharmacology , Energy Metabolism/genetics , Estrogen Receptor beta/genetics , Estrogens/genetics , Estrogens/metabolism , Female , Glucose Tolerance Test , Humans , Male , Mice , Mitochondria/genetics , Mitochondria/metabolism , Receptors, Adrenergic, beta-3/genetics , Receptors, Adrenergic, beta-3/metabolism , Sex Characteristics
7.
Surg Obes Relat Dis ; 16(12): 1910-1918, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1454528

ABSTRACT

BACKGROUND: Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves metabolic homeostasis by modulating energy expenditure and enhancing thermogenesis through increasing the expression level of meteorin-like protein (METRNL) and fibronectin type III domain-containing protein 5 (FNDC5/Irisin) through uncoupling proteins 1/2/3 (UCP1, UCP2, and UCP3). OBJECTIVES: To study the effect of SG on the levels of proteins involved in thermogenesis process. SETTING: Laboratory rats at Kuwait University. METHODS: Male Sprague-Dawley rats, aged 4 to 5 weeks, were divided into 2 groups, control (n = 11) and diet-induced obesity (DIO) (n = 22). The control group was fed regular rat chow ad libitum, whereas the DIO group was fed cafeteria diet "high-fat/carbohydrate diet" ad libitum. At 21 weeks, rats in the DIO group that weighed 20% more than the control group animals underwent surgery. These rats were randomly subdivided into Sham and SG operation groups. Gene expression was evaluated, and enzyme-linked immunosorbent assays were employed to assess the changes in gene and protein levels in tissue and circulation. RESULTS: The protein expression data revealed an increase in METRNL levels in the muscles and white adipose tissue of SG animals. METRNL level in circulation in SG animals was reduced compared with control and Sham rats. The level of Irisin increased in the muscle of SG animals compared with the control and Sham group animals; however, a decrease in Irisin level was observed in the white adipose tissue and brown adipose tissue of SG animals compared with controls. Gene expression analysis revealed decreased METRNL levels in muscle tissues in the SG group compared with the control group animals. Increased expression of FNDC5 (Irisin), UCP2, and UCP3 in the muscle tissue of SG animals was also observed. Furthermore, the levels of UCP1, UCP2, UCP3, and METRNL in the brown adipose tissue of SG animals were upregulated. No significant alteration in the gene expression of Irisin was observed in brown adipose tissue. CONCLUSIONS: Sleeve gastrectomy induces weight loss through complex mechanisms that may include browning of fat.


Subject(s)
Adipose Tissue, Brown , Obesity , Adipose Tissue/metabolism , Animals , Diet , Fibronectins/genetics , Fibronectins/metabolism , Gastrectomy , Kuwait , Male , Mitochondrial Uncoupling Proteins , Muscles/metabolism , Obesity/genetics , Obesity/surgery , Rats , Rats, Sprague-Dawley
8.
Cells ; 10(9)2021 09 09.
Article in English | MEDLINE | ID: covidwho-1408628

ABSTRACT

The present study sought to identify gene networks that are hallmarks of the developing inguinal subcutaneous adipose tissue (iWAT) and the interscapular brown adipose tissue (BAT) in the mouse. RNA profiling revealed that the iWAT of postnatal (P) day 6 mice expressed thermogenic and lipid catabolism transcripts, along with the abundance of transcripts associated with the beige adipogenesis program. This was an unexpected finding, as thermogenic BAT was believed to be the only site of nonshivering thermogenesis in the young mouse. However, the transcriptional landscape of BAT in P6 mice suggests that it is still undergoing differentiation and maturation, and that the iWAT temporally adopts thermogenic and lipolytic potential. Moreover, P6 iWAT and adult (P56) BAT were similar in their expression of immune gene networks, but P6 iWAT was unique in the abundant expression of antimicrobial proteins and virus entry factors, including a possible receptor for SARS-CoV-2. In summary, postnatal iWAT development is associated with a metabolic shift from thermogenesis and lipolysis towards fat storage. However, transcripts of beige-inducing signal pathways including ß-adrenergic receptors and interleukin-4 signaling were underrepresented in young iWAT, suggesting that the signals for thermogenic fat differentiation may be different in early postnatal life and in adulthood.


Subject(s)
Adipocytes, Beige/metabolism , Transcription, Genetic , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Animals , Animals, Newborn , Biomarkers/metabolism , Cell Cycle/genetics , Gene Expression Regulation, Developmental , Gene Ontology , Gene Regulatory Networks , Male , Mice, Inbred C57BL , Models, Biological , Muscle Development/genetics , Neuropeptides/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction
9.
Int J Mol Sci ; 22(15)2021 Jul 31.
Article in English | MEDLINE | ID: covidwho-1346501

ABSTRACT

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.


Subject(s)
Anti-Obesity Agents/therapeutic use , Arachidonic Acids/therapeutic use , Benzoates/therapeutic use , Obesity/drug therapy , Phenylurea Compounds/therapeutic use , Adipogenesis , Adipose Tissue, Brown/cytology , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Animals , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/pharmacology , Arachidonic Acids/administration & dosage , Arachidonic Acids/pharmacology , Benzoates/administration & dosage , Benzoates/pharmacology , Blood Glucose/metabolism , Carnitine O-Palmitoyltransferase/metabolism , Diet, High-Fat , Epoxide Hydrolases/antagonists & inhibitors , Fatty Acids/metabolism , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Obesity/etiology , Obesity/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/pharmacology
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