Milk fat globule membrane and its component phosphatidylcholine induce adipose browning both in vivo and in vitro

The functional induction of brown-like adipocytes in white adipose tissue (WAT) provides a defense against obesity. The aim of this study was to analyze the effects of milk fat globule membrane (MFGM) and its component phosphatidylcholine (PC) on the brown remodeling of WAT. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks and then fed HFD for another 8 weeks with MFGM. In vitro studies were performed in C3H10T1/2 pluripotent stem cells, 3T3-L1 pre-adipocytes and differentiated inguinal WAT stromal vascular cells (SVCs) to determine the role of MFGM and PC on the formation of brown-like adipocytes. MFGM decreased fasting glucose and serum insulin levels in HFD-fed mice. MFGM improved glucose tolerance and insulin sensitivity, and induced browning of inguinal WAT. MFGM and its component PC stimulated transformation of brown-like adipocytes in C3H10T1/2 pluripotent stem cells, 3T3-L1 adipocytes and SVCs by increasing the protein expression of UCP1, PGC-1α, PRDM16 as well as the mRNA expression of other thermogenic genes and beige cell markers. MFGM and PC also increased mitochondrial DNA (mtDNA) copy number, mitochondrial density and oxygen consumption rate and up-regulated the mRNA expression of mitochondria-biogenesis-related genes in vitro. PPARα inhibitor GW6471 treatment or knockdown of PPARα using lentivirus-expressing shRNA inhibited the PC-induced increase in the protein expression of UCP1, PGC-1α and PRDM16 in C3H10T1/2 pluripotent stem cells and 3T3-L1 adipocytes, indicating the potential role of PPARα in PC-mediated brown-like adipocyte formation. In conclusion, MFGM and milk PC induced adipose browning, which has major protective effects against obesity and metabolic dysfunction.     

Lycopene attenuates body weight gain through induction of browning via regulation of peroxisome proliferator-activated receptor γ in high-fat diet-induced obese mice

Lycopene (LYC), one of the major carotenoids in tomatoes, has been preclinically and clinically used to obesity and type 2 diabetes management. However, whether its ability of countering body weight gain is related to induction of brown-like adipocyte phenotype in white adipose tissues (WAT) remains largely unknown. Activation of peroxisome proliferator-activated receptor γ (PPARγ) serves the brown-like phenotype conversion and energy expenditure. Here, we show that LYC treatment promotes glucose consumption and improves insulin sensitivity, as well as fosters white adipocytes browning through up-regulating mRNA and protein expression levels of PPARγ, uncoupling protein 1, PPARγ coactivator-1α and PR domain-containing 16 in the differentiated 3T3-L1 adipocytes and primary adipocytes, as well as in the WAT of HFD-exposed obese mice. In addition, LYC treatment attenuates body weight gain and improves serum lipid profiles as well as promotes brown adipose tissue activation in obese mice. Moreover, PPARγ is induced with LYC intervention in mitochondria respiration and browning in white adipocytes and tissues. Taken together, these results suggest that LYC counteracts obesity and improves glucose and lipid metabolism through induction of the browning via up-regulation of PPARγ, which offers a new perspective of this compound to combat obesity and obesity-related disorders.     

Raspberry ketone induces brown-like adipocyte formation through suppression of autophagy in adipocytes and adipose tissue

Promoting white adipose tissue (WAT) to acquire brown-like characteristics is a promising approach for obesity treatment. Although raspberry ketone (RK) has been reported to possess antiobesity activity, its effects on the formation of brown-like adipocytes remain unclear. Therefore, we investigated the effects and underlying mechanism of RK on WAT browning in 3T3-L1 adipocytes and rats with ovariectomy (Ovx)-induced obesity. RK (100 μM) significantly induced browning of 3T3-L1 cells by increasing mitochondrial biogenesis and the expression of browning-specific proteins (PR domain containing 16, PRDM16; peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC-1α; uncoupling protein-1, UCP-1) and lipolytic enzymes (hormone-sensitive lipase and adipose triglyceride lipase). RK significantly reduced the expression of the autophagy-related protein Atg12 and increased the expression of p62 and heme oxygenase 1 (HO-1). Additionally, these effects of RK were reversed by the HO-1 inhibitor SnPP (20 μM). In addition, RK (160 mg/kg, gavage, for 8 weeks) significantly reduced body weight gain (Ovx+RK, 191.8 ± 4.6 g vs. Ovx, 223.6 ± 5.9; P < .05), food intake, the amount of inguinal adipose tissue (Ovx+RK, 9.05 ± 1.1 g vs Ovx, 12.9 ± 0.92 g; P < .05) and the size of white adipocytes in Ovx rats. Moreover, compared to expression in the Ovx group, the levels of browning-specific proteins were significantly higher and the levels of autophagy-related proteins were significantly lower in the Ovx+RK group. Therefore, this study elucidated the mechanism associated with RK-induced WAT browning and thus provides evidence to support the clinical use of RK for obesity treatment.     

Increasing cAMP levels of preadipocytes by cyanidin-3-glucoside treatment induces the formation of beige phenotypes in 3T3-L1 adipocytes

Obesity is a serious health problem and a major risk factor for the onset of several diseases such as heart disease, diabetes, stroke and cancer. The conversion of white adipocytes to brown-like adipocytes, also called beige or brite adipocytes, by pharmacological and dietary compounds has gained attention as an effective treatment for obesity. Cyanidin-3-glucoside (Cy3G), a polyphenolic compound contained in black soybean, blueberry and grape, has several antiobesity effects. However, there are no reports on the role of Cy3G in the induction of differentiation of preadipocytes to beige adipocytes and corresponding phenotypes. Here, the formation of beige adipocyte phenotypes following treatment with Cy3G was evaluated using 3T3-L1 adipocytes. Cy3G induced phenotypic changes to white adipocytes, such as increased multilocular lipid droplets and mitochondrial content. Additionally, the expression of mitochondrial genes (TFAM, SOD2, UCP-1 and UCP-2), UCP-1 protein and beige adipocyte markers (CITED1 and TBX1) in 3T3-L1 adipocytes was increased by Cy3G. Furthermore, Cy3G promoted preadipocyte differentiation by up-regulating of C/EBPβ through the elevation of the intracellular cAMP levels. These results indicated that Cy3G elevates the intracellular cAMP levels, which induces beige adipocyte phenotypes. This is the first report on the effect of Cy3G on induction of differentiation of preadipocytes into beige adipocyte phenotypes.     

白藜芦醇抑制小鼠肥胖的功效及相关机制探讨

目的:研究白藜芦醇抑制高脂引起的肥胖的作用机制。方法:将18只C57小鼠随机分为3组,分别为对照组、高脂以及高脂+白藜芦醇小鼠模型,给小鼠喂养一定剂量白藜芦醇(100 mg/kg/d),喂养12周。提取小鼠皮下脂肪细胞,分化成熟,加入白藜芦醇,采用q RT-PCR以及Western blot等方法检测HO-1以及棕色脂肪标志基因的表达。通过q RT-PCR检测小鼠脂肪组织炎症因子、UCP-1以及HO-1的表达。结果:白藜芦醇在体内可以明显抑制高脂引起的肥胖,糖耐量异常,同时促进棕色脂肪标志基因UCP-1,PGC-1以及PRDM16的表达。白藜芦醇还可抑制肥胖小鼠脂肪组织炎症因子的增加以及抗炎蛋白HO-1的表达。在体外分化的成熟的皮下脂肪细胞中,白藜芦醇同样可以促进棕色脂肪标志基因UCP-1,PGC-1以及PRDM16的表达。白藜芦醇通过促进抗炎蛋白HO-1的表达抑制高脂引起的脂肪炎症反应。结论:白藜芦醇可以通过促进白色脂肪棕色化以及抑制慢性低度炎症抑制高脂引起的肥胖、糖耐量异常以及改善胰岛素敏感性。     

DHEA administration increases brown fat uncoupling protein 1 levels in obese OLETF rats

We found that UCP-1 and UCP-3 mRNA expression levels and the UCP-1 protein content in brown adipose tissue (BAT) were reduced in prediabetic OLETF rats than the lean LETO rats. Administration of dehydroepiandrosterone (DHEA) for 17 days induced remarkable weight loss, which was in part attributed to an enhanced utilization of ingested energy. DHEA administration significantly increased the levels of BAT UCP-1 and UCP-3 mRNA expression. Among the upstream signals for UCP-1 regulation, expression levels of the beta 3 adrenergic receptor (beta(3)AR) and PPAR gamma coactivator-1 (PGC-1) were significantly decreased in the OLETF rats and increased by DHEA administration. The decreased expression levels of UCP-1 and its upstream regulators, beta(3)AR and PGC-1, in BAT may contribute to inefficient energy utilization and obesity in OLETF rats, which was corrected by DHEA treatment.     

Morphological and receptorial changes in the epididymal adipose tissue of rats subjected to a stressful stimulus

Obesity is nowadays related to other pathological conditions such as inflammation, insulin resistance, and diabetes, but little is known about the relationship between psychological stress and adipocytes. We decided to study the expression of the translocator protein (TSPO) 18-kDa, peroxisome proliferator-activated receptor-γ (PPAR-γ), mitochondrial uncoupling protein-1 (UCP-1), and adipocyte morphology in the adipose tissue of rats subjected to stress conditions. In our model of stress, rats fasted for 24 h were placed in a restraint cage and then immersed vertically to the level of the xiphoid process in a water bath at 23 °C for 7 h. After that period, we removed the epididymal adipose tissues for the subsequent analysis. The optical and electron microscopy revealed that adipocytes of control rats formed a continuous epithelial-like cell layer; on the contrary in the adipocytes of stressed rats some cells have merged together and the number of vessels formed seems to increase. Stressed adipocytes presented unilocular cells with numerous mitochondria with a morphology ranging between that of brown adipose tissue (BAT) and white adipose tissue (WAT). Interestingly, when we investigated the subcellular distribution of UCP-1 by immunogold electron microscopy, the adipose tissue of stressed rats was positive for UCP-1. From the immunoblot analysis with anti-PPAR-γ antibody, we observed an increased expression of PPAR-γ in the adipocytes of stressed group compared with control group (P < 0.05). Stress induced the expression of TSPO 18-kDa receptor (B(max) = 106.45 ± 5.87 fmol/mg proteins), which is undetectable by saturation-binding assay with [(3)H]PK 11195 in the control group.     

Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes

Uncoupling protein (UCP)-1 expressed in brown adipose tissue plays an important role in thermogenesis. Recent data suggest that brown-like adipocytes in white adipose tissue (WAT) and skeletal muscle play a crucial role in the regulation of body weight. Understanding of the mechanism underlying the increase in UCP-1 expression level in these organs should, therefore, provide an approach to managing obesity. The thyroid hormone (TH) has profound effects on mitochondrial biogenesis and promotes the mRNA expression of UCP in skeletal muscle and brown adipose tissue. However, the action of TH on the induction of brown-like adipocytes in WAT has not been elucidated. Thus we investigate whether TH could regulate UCP-1 expression in WAT using multipotent cells isolated from human adipose tissue. In this study, triiodothyronine (T(3)) treatment induced UCP-1 expression and mitochondrial biogenesis, accompanied by the induction of the CCAAT/enhancer binding protein, peroxisome proliferator-activated receptor-γ coactivator-1α, and nuclear respiratory factor-1 in differentiated human multipotent adipose-derived stem cells. The effects of T(3) on UCP-1 induction were dependent on TH receptor-β. Moreover, T(3) treatment increased oxygen consumption rate. These findings indicate that T(3) is an active modulator, which induces energy utilization in white adipocytes through the regulation of UCP-1 expression and mitochondrial biogenesis. Our findings provide evidence that T(3) serves as a bipotential mediator of mitochondrial biogenesis.     

Quercetin attenuates adipose hypertrophy,in part through activation of adipogenesis in rats fed a high-fat diet

An impaired capacity of adipose tissue expansion leads to adipocyte hypertrophy, inflammation and insulin resistance (IR) under positive energy balance. We previously showed that a grape pomace extract, rich in flavonoids including quercetin (Q), attenuates adipose hypertrophy. This study investigated whether dietary Q supplementation promotes adipogenesis in the epididymal white adipose tissue (eWAT) of rats consuming a high-fat diet, characterizing key adipogenic regulators in 3T3-L1 pre-adipocytes. Consumption of a high-fat diet for 6 weeks caused IR, increased plasma TNFα concentrations, eWAT weight, adipocyte size and the eWAT/brown adipose tissue (BAT) ratio. These changes were accompanied by decreased levels of proteins involved in angiogenesis, VEGF-A and its receptor 2 (VEGF-R2), and of two central adipogenic regulators, i.e. PPARγ and C/EBPα, and proteins involved in mature adipocyte formation, i.e. fatty acid synthase (FAS) and adiponectin. Q significantly reduced adipocyte size and enhanced angiogenesis and adipogenesis without changes in eWAT weight and attenuated systemic IR and inflammation. In addition, high-fat diet consumption increased eWAT hypoxia inducible factor-1 alpha (HIF-1α) levels and those of proteins involved in adipose inflammation (TLR-4, CD68, MCP-1, JNK) and activation of endoplasmic reticulum (ER) stress, i.e. ATF-6 and XBP-1. Q mitigated all these events. Q and quercetin 3-glucoronide prevented TNFα-mediated downregulation of adipogenesis during 3T3-L1 pre-adipocytes early differentiation. Together, Q capacity to promote a healthy adipose expansion enhancing angiogenesis and adipogenesis may contribute to reduced adipose hypertrophy, inflammation and IR. Consumption of diets rich in Q could be useful to counteract the adverse effects of high-fat diet-induced adipose dysfunction.     

CD38 deficiency suppresses adipogenesis and lipogenesis in adipose tissues through activating Sirt1/PPARγ signaling pathway

It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38‐deficient mice were resistant to high‐fat diet (HFD)‐induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38^?/? and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38^?/? mice, 3T3‐L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD‐fed mice or the MEFs, 3T3‐L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38^?/? male mice were significantly resistant to HFD‐induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3‐L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/EBPα were markedly attenuated in adipocytes from HFD‐fed CD38^?/? mice and CD38^?/? MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38^?/? MEFs. Finally, the CD38 deficiency‐mediated activations of Sirt1 signalling were up‐regulated or down‐regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/PPARγ‐FASN signalling pathway during the development of obesity.     

Vanillin induces adipocyte differentiation in 3T3-L1 cells by activating extracellular signal regulated kinase 42/44

AimsTo investigate the effect of vanillin, a dietary component, on adipocyte differentiation and the mechanism involved in the process using 3T3-L1 murine preadipocytes.Main methodsThe effect of vanillin on adipocyte differentiation was detected by Oil Red O analysis. The activation of extracellular signal regulated kinase 42/44 (ERK 42/44), Akt, expression of the key regulator of adipocyte differentiation peroxisome proliferators-activated receptor (PPARγ) and its target gene glucose transporter 4 (GLUT4) were detected by western blotting. Glucose uptake assay was used to determine the insulin sensitivity of adipocytes differentiated by vanillin treatment. To confirm the role of ERK 42/44 and Akt, Oil Red O analysis was performed with cells differentiated in the presence or absence of ERK inhibitor U0126 or Akt kinase 1/2 inhibitor.Key findingsVanillin induced adipocyte differentiation in 3T3-L1 cells in a dose dependent manner and also increased the expression levels of PPARγ and its target gene GLUT4. The adipocytes differentiated by vanillin exhibited insulin sensitivity as demonstrated by a significant increase in glucose uptake. Vanillin treatment activated the phosphorylation of ERK 42/44 during the initial phase of adipocyte differentiation but there was no significant change in the Akt phosphorylation status.SignificanceThe data show that vanillin induces adipocyte differentiation in 3T3-L1 cells by activating ERK42/44 and these adipocytes are insulin sensitive in nature.     

N-butylidenephthalide ameliorates high-fat diet-induced obesity in mice and promotes browning through adrenergic response/AMPK activation in mouse beige adipocytes

Thermogenesis (non-exercise activity) in brown adipose tissue (BAT) promotes energy expenditure because of its higher number of mitochondria than white adipose tissue (WAT). The main function of thermogenesis in BAT can counteract obesity through the dissipation of calories as heat. N-butylidenephthalide (BP) is a natural derivative from Angelica sinensis, a Chinese herb that has been used for thousands of years. In this report, we demonstrated that BP improved the metabolic profiles of mice with high fat diet-induced obesity (DIO) by preventing weight gain, improving serum blood parameters, enhancing energy expenditure, stimulating white fat browning, and reversing hepatic steatosis. Further investigations demonstrated that BP administration upregulated the mRNA expression of beige (CD137, TMEM26) and brown fat selected genes (UCP1, PRDM16, PGC-1α, PPARγ) in white adipose tissues. In vitro studies, BP treatment increased multilocular lipid droplet levels, induced β-adrenergic receptor (cAMP/PKA) and AMP-activated protein kinase (AMPK) signaling (AMPK/acetyl-CoA carboxylase/SIRT1), and increased oxygen consumption in murine differentiated beige adipocytes, and the effects of BP were blocked by an AMPK inhibitor. BP promoted the interaction of AMPK with PGC-1α in beige adipocytes. Our findings provide novel insights into the application of BP in regulating energy metabolism and suggest its utility for clinical use in the treatment of obesity and related diseases.     

Roles for peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivators 1α and 1β in regulating response of white and brown adipocytes to hypoxia

Obese white adipose tissue is hypoxic but is incapable of inducing compensatory angiogenesis. Brown adipose tissue is highly vascularized, facilitating delivery of nutrients to brown adipocytes for heat production. In this study, we investigated the mechanisms by which white and brown adipocytes respond to hypoxia. Brown adipocytes produced lower amounts of hypoxia-inducible factor 1α (HIF-1α) than white adipocytes in response to low O(2) but induced higher levels of hypoxia-associated genes. The response of white adipocytes to hypoxia required HIF-1α, but its presence alone was incapable of inducing target gene expression under normoxic conditions. In addition to the HIF-1α targets, hypoxia also induced many inflammatory genes. Exposure of white adipocytes to a peroxisome proliferator-activated receptor γ (PPARγ) ligand (troglitazone) attenuated induction of these genes but enhanced expression of the HIF-1α targets. Knockdown of PPARγ in mature white adipocytes prevented the usual robust induction of HIF-1α targets in response to hypoxia. Similarly, knockdown of PPARγ coactivator (PGC) 1β in PGC-1α-deficient brown adipocytes eliminated their response to hypoxia. These data demonstrate that the response of white adipocytes requires HIF-1α but also depends on PPARγ in white cells and the PPARγ cofactors PGC-1α and PGC-1β in brown cells.     

Impact of physical exercise on visceral adipose tissue fatty acid profile and inflammation in response to a high-fat diet regimen

PurposeStudies associate specific fatty-acids (FA) with the pathophysiology of inflammation. We aimed to analyze the impact of exercise on adipose tissue FA profile in response to a high-fat diet (HFD) and to ascertain whether these exercise-induced changes in specific FA have repercussions on obesity-related inflammation.MethodsSprague-Dawley rats were assigned into sedentary, voluntary physical-activity (VPA) and endurance training (ET) groups fed a standard (S, 35kcal% fat) or high-fat (71kcal% fat) diets. VPA-animals had unrestricted access to wheel-running. After 9-wks, ET-animals engaged a running protocol for 8-wks, while maintained dietary treatments. The FA content in epididymal white-adipose tissue (eWAT) triglycerides was analyzed by gas-chromatography and the expression of inflammatory markers was determined using RT-qPCR, Western and slot blotting.ResultsEight-wks of ET reversed obesity-related anatomical features. HFD increased plasma tumor necrosis factor (TNF)-α content and eWAT monocyte chemoattractant protein (MCP)-1 protein expression. HFD decreased eWAT content of saturated FA and monounsaturated FA, while increased linoleic acid and prostaglandin E2 (PGE2) levels in eWAT. VPA decreased visceral adiposity, adipocyte size and MCP-1 in HFD-fed animals. The VPA and ET interventions diminished palmitoleic acid and increased linoleic acid in HFD-fed groups. Moreover, both interventions increased PGE2 levels in standard diet-fed groups and decreased in HFD. ET increased eWAT fatty acid desaturase 1 (FADS1) and elongase 5 (ELOVL5) protein content in both diet types. ET reduced eWAT inflammatory markers (TNF-α, IL-6), macrophage recruitment (MCP-1 and F4/80) and increased IL-10/TNF-α ratio in plasma and in eWAT in both diet types.ConclusionsExercise induced FA-specific changes independently of dietary FA composition, but only ET attenuated the inflammatory response in VAT of HFD-fed rats. Moreover, the exercise-induced FA changes did not correlate with the inflammatory response in VAT of rats submitted to HFD.     

Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance

Peroxisome proliferator-activated receptor gamma (PPAR gamma) co-activator 1 (PGC-1) regulates glucose metabolism and energy expenditure and, thus, potentially insulin sensitivity. We examined the expression of PGC-1, PPAR gamma, insulin receptor substrate-1 (IRS-1), glucose transporter isoform-4 (GLUT-4), and mitochondrial uncoupling protein-1 (UCP-1) in adipose tissue and skeletal muscle from non-obese, non-diabetic insulin-resistant, and insulin-sensitive individuals. PGC-1, both mRNA and protein, was expressed in human adipose tissue and the expression was significantly reduced in insulin-resistant subjects. The expression of PGC-1 correlated with the mRNA levels of IRS-1, GLUT-4, and UCP-1 in adipose tissue. Furthermore, the adipose tissue expression of PGC-1 and IRS-1 correlated with insulin action in vivo. In contrast, no differential expression of PGC-1, GLUT-4, or IRS-1 was found in the skeletal muscle of insulin-resistant vs insulin-sensitive subjects. The findings suggest that PGC-1 may be involved in the differential gene expression and regulation between adipose tissue and skeletal muscle. The combined reduction of PGC-1 and insulin signaling molecules in adipose tissue implicates adipose tissue dysfunction which, in turn, can impair the systemic insulin response in the insulin-resistant subjects.     

Serum amyloid A induces lipolysis by downregulating perilipin through ERK1/2 and PKA signaling pathways

Serum amyloid A (SAA) is not only an apolipoprotein, but also a member of the adipokine family with potential to enhance lipolysis. The purpose of this study was to explore how SAA facilitates lipolysis in porcine adipocytes. We found that SAA increased the phosphorylation of perilipin and hormone-sensitive lipase (HSL) after 12-h treatment and decreased perilipin expression after 24-h treatment, and these effects were prevented by extracellular signal-regulated kinase (ERK) or protein kinase A (PKA) inhibitors in primary adipocyte cell culture. SAA treatment decreased HSL and adipose triglyceride lipase (ATGL) expression. SAA treatment also activated ERK and PKA by increasing the phosphorylation of these kinases. Moreover, SAA significantly increased porcine adipocyte glycerol release and lipase activity, which was inhibited by either ERK (PD98059) or PKA (H89) inhibitors, suggesting that ERK and PKA were involved in mediating SAA enhanced lipolysis. SAA downregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) mRNA, which was reversed by the ERK inhibitor. We performed a porcine perilipin promoter assay in differentiated 3T3-L1 adipocytes and found that SAA reduced the porcine perilipin promoter specifically through the function of its PPAR response element (PPRE), and this effect was reversed by the ERK inhibitor. These findings demonstrate that SAA-induced lipolysis is a result of downregulation of perilipin and activation of HSL via ERK/PPARγ and PKA signaling pathways. The finding could lead to developing new strategies for reducing human obesity.