Compression Properties of Fat Layer under Impact Loading / 医用生物力学

Objective To study dynamic compression performance of adipose tissues, so as to further reveal the damage mechanism, and provide references for medical treatment.Methods Based on the improved split Hopkinson pressure bar (SHPB) experimental device, the adipose tissue dynamic compression experiment was conducted. The stress-strain curves of adipose tissues at different strain rates were obtained. Then the numerical model of SHPB was established, and the experimental process was simulated and analyzed. The numerical simulation for penetration process of 32 mm diameter rubber non-lethal projectile into the simulated target in human abdomen was carried out.Results Adipose tissues had a noticeable strain rate effect. The stress-strain curves at two high strain rates were approximately straight lines. The slope was similar, and the elastic modulus was 3.25 MPa, which was about 6 times of that under a quasi-static state. The simulation curves of fat SHPB were consistent with the experimental curves, which verified correctness of the constitutive model. In the process of non-lethal projectile penetrating human abdomen, an annular convex area similar to water wave appeared on skin surface, and the fat layer absorbed about 67% of the impact kinetic energy.Conclusions The experimental data of adipose tissues are very accurate. Numerical simulation can reproduce the penetration process well, and provide references for studying the damaging effect of non-lethal weapons on human body.

Reverse and Optimization for Constitutive Parameters of Adipose Tissues Based on Feasible Direction Method / 医用生物力学

Objective To study the constitutive model of adipose tissue at medium strain rate and its parameter inversion. Methods Based on experiments of adipose tissue mechanical properties, the compression experiment of adipose tissues was reconstructed by finite element method, and the parameters for characterizing constitutive models of adipose tissues were screened. Combined with the method of feasible direction (MFD) in optimization method, the reverse calculation for parameters of fat tissue constitutive model at medium strain rate was conducted. ResultsCompared with Ogden constitutive model, the viscoelastic constitutive model was more suitable for characterizing the mechanical response at medium strain rate (260 s-1). The parameters of the constitutive model suitable for simulation were obtained using the reverse method. Conclusions The viscoelastic constitutive model was more suitable for characterizing the mechanical response at medium strain rate. The results provide references for studying the influence of human adipose tissues on body injury in finite element simulation of vehicle collisions.

Research progress on whitening of brown adipose tissues / 中国药理学通报

Brown adipose tissues can consume energy by generating heat. The whitening of BAT will damage its thermogenic function and cause diseases related to obesity and metabolic disorders. It is of great significance to slow down or inhibit the process of BAT whitening. This article reviews the inducing factorsand the key regulators of brown adipose tissue whitening, hoping to provide some ideas for the prevention and treatment of obesity and metabolic disorders.

Effect of cold exposure on browning of white adipose tissues in mice fed with high fat diet / 中国药理学通报

Aim: To observe the effect of cold exposure on browning of white adipose tissues in mice fed with high fat diet. Methods: Male 8-week-old C57BL/6J mice were randomly divided into HFD + 5 °C group and HFD + RT group, after 8 weeks of high-fat diet. Male 8-week-old C57BL/6J mice were randomly divided into normal + 5 °C group and normal + RT group, after 8 weeks of normal diet. Each group of mice were intervened for 2 h at different temperatures in the same time period for 8 weeks. Parameters, including body weight, food intake, inguinal white adipose tissue (iWAT) mass, brown adipose tissue (BAT) mass, blood glucose, blood lipids, leptin, adiponectin, adipose tissue pathology and in situ expression of uncoupling protein 1(UCP1) and prohibitin protein (PHB) in iWAT and BAT. Results: Compared with HFD + RT group, cold exposure not only significantly reduced body weight, blood glucose, iWAT weight/body weight ratio, TC, TG, LDL-C and leptin, but also increased food intake and BAT weight in high-fat diet mice. HE staining showed that iWAT and BAT cells became smaller and had multiple compartments. The iWAT had a browning trend. Immunohistochemistry showed that UCP1 and PHB protein in iWAT and BAT significantly increased. Conclusions: Cold exposure can counteract the weight gain caused by a high-fat diet, which may be related to the activation of brown adipose tissue and the induction of browning of white adipose tissues, increasing heat production and reducing white fat accumulation.

Dihydromyricetin promoted browning of subscapular adipose tissues in obese mice fed with high-fat diet via activating AMPK-PGC1 a-Sirtl signaling pathway / 中国药理学通报

Aim To observe the effect of dihydromyricetin (DHM) on the browning of subscapular adipose tissues in the high-fat diet fed obese mice, and clarify the mechanism. Methods C57BL/6J mice were fed with normal and high-fat diet, and were treated with or without low dose (125 mg • kg"1 • d"1) or high dose (250 mg • kg"1 • d"1) DHM for 16W. The body mass of mice was measured every four weeks during the experiment. After 16 weeks, the mice were fasted overnight. Blood samples were taken for fasting blood glucose. The mice were then sacrificed and the body length measured. The Lee' s index was calculated. The size of the subscapular adipocytes was observed by HE staining. The mRNA and protein expression of uncoupling protein 1 (UCP1) , PR domain containing 16 (Prdml6) , adenylate-activated protein kinase (AMPK) , peroxisome proliferator-activated receptor gamma-assisted activator alpha (PGCla) and silencing signal regulator 1 (Sirtl) were assessed by real time quantitative PCR and Western blot assay. Results Compared with normal control group (ND group) , the body mass of mice in high-fat diet group (HFD group) significantly increased, suggesting that the obese mice model was successfully replicated. In addition , blood glucose, Lee' s index and the fat cell diameter of the subscapular adipose tissues in HFD group all significantly increased, while the mRNA and pro-tein expression of UCP1, Prdml6, AMPK, PGCla and Sirtl significantly decreased. DHM markedly re-versed the changes of the above indexes of HFD mice, but DHM did not significantly affect the above indexes of normal mice. Conclusions Dihydromyricetin promotes the browning of subscapular adipose tissues in mice fed with high-fat diet, which might be via activating AMPK-PGC1 a-Sirtl signaling pathway.

Research progress of mitophagy in adipose tissue / 国际儿科学杂志

Mitophagy is a process that selectively break down the damaged or unwanted mitochondria through autophagy and is a regulatory mechanism for maintaining intracellular mitochondrial quantity and mass balance.Adipose tissue is an important endocrine tissue that maintains energy balance and is generally divided into three types:white adipose tissue,brown adipose tissue and beige adipose tissue.There are specific biological processes in adipocyte differentiation stage that are specifically regulated by autophagy regulators.Mitophagy plays a central role in the function and maintenance of metabolic tissues such as liver,pancreas,and adipose tissues.The specific enhancement or inhibition of mitophagy,may be another new therapeutic direction of obesity,diabetes and other metabolic diseases.This paper reviews the progress between mitophagy and obesity,and its mechanism and regulation.

La tormentosa relación entre las grasas y el desarrollo de la diabetes mellitus tipo 2: actualizado. Parte 2 / The stormy relationship between fats and the development of type 2 diabetes mellitus: Updated. Part 2

En esta parte de la revisión se describe la relación funcional entre el metabolismo de los lípidos y los hidratos de carbono y su interdependencia, desde el ciclo glucosa-ácido grasos y la hipótesis portal de la insulinorresistencia a los nuevos conocimientos sobre los adipocitos marrones y beiges, con énfasis en el normal funcionamiento de un patrón endocrino cuya disfunción es clave en la fisiopatología de la DMT2 y la obesidad. Se discute la ectopia o el asiento de grasa en el tejido magro por incapacidad del tejido adiposo para seguir acopiando lípidos y la actividad endocrina del adipocito, con la producción de moléculas (adipoquinas) que influyen sobre los mecanismos inductores de insulinorresistencia (leptina, adiponectina, TNF-α, resistina, etc.) y disfunción de la célula beta. Se describen la disminución de la capacidad oxidativa en la cadena respiratoria mitocondrial y el renacer del concepto de lipogénesis de novo, ambas favoreciendo el acopie de lípido intracelular. En tejidos magros existen pequeñas reservas intracelulares de lípidos que mantienen la regulación de funciones esenciales, aunque si aparece una sobrecarga lipídica el fenómeno conduciría a una disfunción (lipotoxicidad) y a la muerte celular (lipoapoptosis). La tormentosa relación entre los lípidos y el islote de Langerhans va más allá del esfuerzo funcional que impone la insulinorresistencia periférica sobre la célula β, por efectos directos de los lípidos o de sus derivados sobre la función del islote pancreático. Sin déficit de insulina no se desarrolla diabetes.

In this part of the review, the functional relationship between lipid and carbohydrate metabolisms and their interdependence is described, from the glucose-fatty acid cycle and the portal hypothesis of insulin resistance to the new knowledge on brown and beige adipocytes, with emphasis on the normal functioning of an endocrine pattern in which its dysfunction is a key factor in the pathophysiology of T2DM and obesity. Ectopic fat deposition in lean tissues due to the inability of the adipose tissue to continuously collect lipids and the endocrine activity of adipocytes is discussed. The production of molecules (adipokines) influencing some of the mechanisms involved in the development of insulin resistance (leptin, adiponectin, TNF-α, resistin, etc.) and beta cell dysfunction is also revisited. The decrease in the oxidative capacity in the mitochondrial respiratory chain and the rebirth of the concept of de novo lipogenesis are described, both effects favouring intracellular lipid accumulation. In lean tissues there are small intracellular lipid reserves that help to maintain the regulation of essential functions; however, when a lipid overload occurs the phenomenon could lead to severe cell dysfunction (lipotoxicity), and death (lipo-apoptosis). The stormy relationship between lipids and the Langerhans' islets goes beyond the functional effort imposed by peripheral insulin-resistance on the β cells, either by the direct effect of lipids or by their derivatives on overall pancreatic islet function. Within a scenario of no insulin deficit, diabetes does not develop.

La tormentosa relación entre las grasas y el desarrollo de la diabetes mellitus de tipo 2: actualizado. Parte 1 / The stormy relationship between fats and the development of type 2 diabetes mellitus: An Update. Part 1

Se describe la relación funcional del metabolismo de las grasas y los hidratos de carbono y su interdependencia, desde los tradicionales conceptos del ciclo glucosa-ácidos grasos (Randle) y la hipótesis portal de la insulinorresistencia hasta los nuevos sobre los adipocitos marrones y beiges, con énfasis en el normal funcionamiento de un patrón endocrino cuya disfunción es clave en la fisiopatología: el eje adipoinsular, vinculado funcionalmente incluso con el hipotálamo, la hipófisis y las adrenales, que involucra 2 hormonas adipogénicas (insulina y glucocorticoide) que facilitarían el desarrollo de la grasa omental perivisceral, con fuertes consecuencias metabólicas. Se discute la ectopia o asiento de grasa en tejido magro por incapacidad del tejido adiposo para seguir atesorando grasas y la actividad endocrina del adipocito, con la producción de moléculas que influyen sobre los mecanismos productores de insulinorresistencia (leptina, adiponectina, TNF-α, resistina, etc.) y disfunción insular. Se describe la disminución de la capacidad oxidativa en la cadena respiratoria mitocondrial y el renacer del concepto de lipogénesis de novo, ambas favorecedoras del atesoramiento de grasas intracelular. En tejidos magros existen pequeñas reservas intracelulares de grasas que mantienen una regulación de funciones esenciales, aunque si aparece una sobrecarga lipídica, el fenómeno conduciría a disfunción (lipotoxicidad) y muerte celular (lipoapoptosis). La tormentosa relación entre las grasas y el islote de Langerhans va más allá del esfuerzo funcional que impone la insulinorresistencia periférica sobre la célula β, por efectos directos de los lípidos o sus derivados sobre la función del islote pancreático. Sin déficit de insulina no hay diabetes.

A review is presented on a functional relationship between fat and carbohydrate metabolism and inter-dependence from the traditional concepts of glucose-fatty acids cycle (Randle), and from the insulin resistance portal hypothesis up to the new aspects on brown and beige adipocytes. Emphasis is placed on the normal function of an endocrine pattern, in which its malfunction is the key in the pathophysiology of these conditions: the adipoinsular axis, with a functional link with the hypothalamic-pituitary-adrenal axis, which involves 2 adipogenic hormones (insulin and glucocorticoid). This has an influence on the development of omental peri-visceral fat, with severe metabolic consequences. A discussion is also presented on the concept of ectopic fat on non-adipose tissues that results in the incapacity of fatty tissue for storing lipids and the considerations about the endocrine activity of adipocyte producing substances that influence several mechanisms that could result in insulin resistance (leptin, adiponectin, TNF-α, resistin, etc.). New aspects are considered regarding the decrease in the oxidative capacity in the mitochondrial respiratory chain, and the rebirth of the concept of de novo lipogenesis that increases the storing of intra-cellular fat. In non-adipose tissues there are small intra-cellular fat quantities for essential functions, but lipid overloading leads to cell dysfunction (lipo-toxicity) and death (lipo-apoptosis). The stormy relationship between fat and Langerhans' Islets goes beyond the functional effort as consequence of peripheral insulin-resistance and the pancreatic beta cell suffers a direct lipid (or derivatives) functional effect. Without insulin deficiency diabetes does not appear.

The investigation on the inhibitive effect of berberine on gene expression of FSP27 to improve visceral white adipose tissue insulin resistance in type 2 diabetic hamsters / 天津医药

Objective To study the effects of berberine (BBR) on the gene mRNA expression of fat-specific protein 27 (FSP27) and PR domain containing 16 (PRDM16) signal pathway in visceral white adipose tissues (VWAT) from type 2 dia? betic (T2DM) Chinese hamsters, and explore the related mechanisms. Methods The obese insulin-resistant (OIR) hamster model was induced by high-fat diet, and T2DM hamster model was created by OIR hamster model injected with low-dose streptozotocin. The control group was fed with standard laboratory chow. After the induction, the hamsters were randomly di?vided into control, OIR, obese T2DM and BBR-treated T2DM groups. After nine-week BBR treatment, real-time quantita?tive PCR was used to measure the gene mRNA expression changes of VWAT FSP27 and PRDM16 signal pathway and their target genes from different groups. Results Compared with control group, the gene mRNA expressions of PRDM16, CtBP-1, CtBP-2, C/EBPβ, PPARγ, PGC1α, PGC-1β and brown adipose tissue-specific genes such as UCP-1, Cidea, Elovl3, PPARα, and Acox, Cpt1 and Acadm were decreased and that of FSP27 and white adipose tissue-specific genes including Resistin, MEST and Serpina3k were increased in VWAT in OIR and obese T2DM groups. BBR treatment down-regulated FSP27 expression, enhanced PRDM16 signal pathway, and induced the gene mRNA expression of brown adipose tissue-spe?cific genes in VWAT of obese T2DM group to develop browning gene phenotype of VWAT, and then improved fat-induced insulin resistance. Conclusion The decreased FSP27 expression and increased PRDM16 expression are involved in the molecular mechanisms of browning of visceral white adipose tissues induced by BBR, and which contributes to improve ab?normal lipids metabolism and fat-induced insulin resistance in VWAT by enhancing consumption of energy as heat to re?store VWAT function.

Regulations of berberine on gene expression of BMP4 transcriptional pathways to improve visceral white adipose tissues insulin resistance in type 2 diabetic hamsters / 中国中药杂志

To study the effects of berberine on the gene mRNA expressions of BMP4 transcriptional pathways and brown/white adipose tissue conversion transcriptional pathways in visceral white adipose tissues(VWAT) in type 2 diabetic hamsters and explore the relevant mechanisms. The obese insulin-resistant hamster model were induced by using high-fat diet, and then the type 2 diabetic hamster model was created through injection with low-dose streptozotocin in the obese insulin-resistant hamster model. After the modeling, the hamsters were randomly divided into normal control, obese insulin-resistant, type 2 diabetic and berberine-treated diabetic groups. After the nine-week treatment, real-time quantitative PCR was used to measure the changes in gene mRNA expressions of VWAT BMP4 transcriptional pathways, brown/white adipose tissue conversion transcriptional pathways and their target genes in different groups. The results showed that the gene mRNA expressions of BMP4, BMPRⅡ, BMPRlA, Smad1, Smad5, Smad8, p38/MAPK, ATF2, PRDM16, C/EBPβ, PGC1α, PPARγ and brown adipose tissue-specific genes was decreased and that of Smad6, Smurf1 and white adipose tissue-specific genes was increased in VWAT of model hamsters. Treatment with berberine regulated BMP4 transcriptional pathways and brown adipose tissue transcriptional pathways and induced the gene mRNA expression of brown adipose tissue-specific genes in VWAT to develop browning gene phenotype of white adipose tissues, and then improved fat-induced insulin resistance. These findings indicated that BMP4 transcriptional pathways involved in the formation of fat-induced visceral white adipose tissues insulin resistance (FIVWATIR) and the browning molecular mechanism of white adipose tissues induced by berberine.

Role of FAT/CD36 in high-fat diet-induced adipose tissue inflammation / 中国病理生理杂志

AIM: To investigate the role of fatty acid translocase/CD36 (FAT/CD36) in adipose tissue in-flammation induced by a high-fat diet.METHODS:C57BL/6J mice were fed with a normal-chow diet ( NCD) or a high-fat diet ( HFD) for 14 weeks.The content of free fatty acid ( FFA) in the serum was measured by ELISA.The expression of CD36, cytokines and chemokines at mRNA and protein levels in the adipose tissues was determined by real-time poly-merase chain reaction and Western blotting.Immunohistochemical staining was used to examine the macrophages infiltration in the adipose tissues.The inflammatory responses in CD36 knockout mice and wild type mice with high-fat diet were ana-lyzed.RESULTS:The levels of FAT/CD36 were higher in HFD group than that in NCD group.HFD feeding enhanced the mRNA and protein expression of IL-1β, IL-6, TNF-α, MCP-1 and MIP-1, as well as promoted macrophage infiltration in the adipose tissues.Interestingly, as fed with HFD, the expression of cytokines/chemokines and macrophage infiltration were significantly reduced in adipose tissues of the CD36 knockout mice, compared with the wild type mice.CONCLU-SION:High-fat diet promotes adipose tissue inflammation in the mice in a FAT/CD36-dependent manner.

Influence of brown adipose tissue activity on 18F-FDG uptake in tumors / 肿瘤

Objective: To evaluate the influence of BAT (brown adipose tissue) activity on 18F-FDG (18F-fluoro-2-deoxyglucose) uptake in tumors in cancer-bearing mice by using PET/CT (positron emission tomography/computed tomography) imaging. Methods: The model of mice bearing NCI-H1299 human non-small cell lung cancer was established. The activity of BAT in mice was adjusted through regulating the experimental conditions. Two groups were designed in this study, including BAT-activation group (the activity of BAT in mice was stimulated by cold exposure and food diet during the period of 18F-FDG uptake) and BAT-inhibition group (the activity of BAT in mice was inhibited by fasting, anesthesia and heating). The mice were scanned with micro-PET/CT and the uptake of 18F-FDG in tumors in the two groups was analyzed and compared. The SUV (standard uptake value) was calculated. Results: The tumor in BAT-activation group was nearly invisible on PET image and its 18F-FDG uptake value (SUV 0.15±0.06) was significantly lower than that in the BAT-inhibition group (SUV 0.58±0.20) (P < 0.05). Conclusion: The enhancement of BAT activity will significantly decrease the uptake of 18F-FDG in tumors and influence the imaging of the tumors. Copyright © 2013 by TUMOR.

Effects of safflower oil on adipose-associated gene expression in mice / 中华内分泌代谢杂志

Seventy C57BL/6 mice were divided into control group,lard group,lard transferred into safflower oil group,and safflower oil group.After 20 weeks,the white adipose tissues were taken to analyse the gene differentiational expression prolife.The results showed that body weight,blood glucose and lipids,and insulin levels in lard group were higher than those in control group( all P＜0.05 ),which were decreased after lard was transferred into safflower oil for 10 weeks( all P＜0.05 ).Safflower oil regulated some of the orexigenic genes,anorectic genes,and the genes involved in energy expenditure in adipose tissues such as opioid receptor,glucagon,and PPARα.

Osteogenic potential of hBMP-2 gene transduced human adipose-derived stem cells / 中华创伤杂志

Objective To investigate the ostengenie potential of adipose-derived stem cells(AD- SCs)when exposed to adenovirns containing hBMP-2 cDNA(Adv-hBMP-2)and offer a choice of cell source for gene therapy and tissue engineering.Methods Human adipose tissues were obtained from patients who received orthopaedic surgery or liposuction.ADSCs were obtained by digesting the adipose tissues.Firstly,flowcytometric analysis was performed for the confirmation of mesenchymal stem cell ori- gin and the surface markers including CD34,CD44,CD68,CD71,CD90,and CD105.The ADSCs were transfected by Adv-hBMP-2 and the effects were tested in vitro,lmmunoprecipitation and Western blotting and ELISA were performed for confirming BMP gone transduction and its stable expression.The transform of ADSCs was assessed by extracellular ALP staining,intracellular ALP spectrophotometry,von Kossa staining and RT-PCR.In the in vivo experiment ADSC-Adv-hBMP-2 cells were injected into the hind limb of nude mice and analyzed radiographically and histologically.Results ADSCs were successfully isolated from human adipose tissues.The isolated ADSCs expressed CD44,CD71,CD90 and CD105 and CD34 and CD68 were absent.The result confirmed the mesenchymal stem cell origin of the cells.West- ern blotting and ELISA confirmed successful and persistent hBMP-2 production by ADSC-Adv-hBMP-2 cells.Extracellular ALP staining,intracellular ALP spectrophotometry,yon Kossa staining and RT-PCR revealed that ADSCs treated with Adv-hBMP-2 had a tendency of transfering into osteoblast.X-ray and H&E sections from hind limb of nude mice injected with ADSC-Adv-hBMP-2 cells confirmed bone forma- tion at 2 weeks.Conclusions Liposuction aspirates contain abundant ADSCs that can be transduced with hBMP-2 gene,and the tranduced ADSCs differentiate into the osteoblast.ADSCs may be an ideal source of mesenchyme-lineage stem cells for gone therapy and tissue engineering.