Gomisin A Alleviates Obesity by Regulating the Phenotypic Switch between White and Brown Adipocytes

2021 ◽  
Vol 49 (08) ◽  
pp. 1929-1948
Author(s):  
Yo-Han Han ◽  
Ji-Ye Kee ◽  
Seung-Heon Hong
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Uncoupling Protein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Weight Changes ◽  
Brown Adipocytes ◽  
Phenotypic Changes ◽  
Brown Adipose ◽  
Gomisin A

Although gomisin A (GA) alleviates cancer and inflammation, its anti-obesity effect and the underlying mechanism have not yet been elucidated. Therefore, in this study, we aimed to elucidate the anti-obesity effects of GA by investigating the phenotypic changes involved in the browning and whitening of adipocytes. Here, obesity was induced to C57BL/6J mice using a high-fat diet (HFD). We administrated GA and checked weight changes for 12 weeks. We found that GA decreased the weight of weight gain, epididymal white adipose tissue (eWAT), and liver in the mice. In addition, the administration of GA elevated the levels of high-density lipoprotein (HDL)-cholesterol in the mice serum. Moreover, even after 12 weeks of treatment with GA, it did not cause any hepatic and renal toxicity. However, we found that GA induced the browning of eWAT and inhibited the whitening of brown adipose tissue. We further confirmed the anti-obesity mechanism of GA using 3T3-L1 cells, the human adipose mesenchymal stem cells (hAMSCs), and primary brown adipocytes (BAs) in vitroexperiments. We found that GA suppressed adipogenesis via the activation of AMP-activated protein kinase (AMPK). Furthermore, GA-induced browning by increasing the expression levels of uncoupling protein 1 (UCP1) in hAMSCs. The results of our study indicate that GA can inhibit weight gain by regulating the phenotypic changes involved in the browning and whitening of adipose tissues, which makes it a potential therapeutic agent for the treatment of obesity.

scholarly journals Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

2020 ◽  
Author(s):  
Xuemei Liu ◽  
Xiyu Feng ◽  
Chao Deng ◽  
Lu Liu ◽  
Yanping Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Olanzapine Treatment ◽  
Brown Adipose

Abstract BackgroundPrescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant sedation, weight gain, and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.MethodsTo investigate the efficacy of interventions of statin aimed at reversing SGA-induced dyslipidemia, young Sprague Dawley (SD) rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks.ResultsOlanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but had no significant effect on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. A down-regulating of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) expression was observed in brown adipose tissue (BAT) in the olanzapine-only group, following a significant decrease in the ratio of phosphorylated PKA (p-PKA)/PKA. Interestingly, these protein changes could be reversed by co-treatment with O+B. Our results demonstrated simvastatin to be effective in ameliorating TC and TG elevated by olanzapine.ConclusionsModulation of BAT activity could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.

scholarly journals Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

2020 ◽  
Author(s):  
Xuemei Liu ◽  
Xiyu Feng ◽  
Chao Deng ◽  
Lu Liu ◽  
Yanping Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Olanzapine Treatment ◽  
Brown Adipose

Abstract Background Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.Methods To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks. Results Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O+B. Conclusions Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.

scholarly journals Association of PRDM16 rs12409277 and CtBP2 rs1561589 gene polymorphisms with lipid profile of adolescents

2021 ◽  
Author(s):  
Nela Maksimovic ◽  
Vanja Vidovic ◽  
Tatjana Damnjanovic ◽  
Biljana Jekic ◽  
Nada Majkic Singh ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Fasting Glucose ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Levels ◽  
Brown Adipose

IntroductionPositive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue specific genes through the association with C-terminal binding co-repressor proteins (CtBP1 and CtBP2). In healthy adults presence of BAT has been associated with lower glucose, total cholesterol and LDL (low-density lipoprotein) cholesterol levels. Our aim was to analyze the association of PRDM16 gene (rs12409277) and CtBP2 gene (rs1561589) polymorphisms with body mass index (BMI), fasting glucose level and lipid profile of adolescents.Material and methodsOur study included 295 healthy school children, 145 boys (49.2%) and 150 girls (50.8%), 15 years of age. Genotypes for the selected polymorphisms were detected by the real-time PCR method. Age, gender, height, weight, lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and fasting glucose levels were recorded.ResultsWe did not find a statistically significant association of rs12409277 and rs1561589 polymorphisms with BMI, fasting glucose and lipid profile of adolescents. We further analyzed the combined effect of the two SNPs and the statistical analysis showed that carriers of CT genotype of rs12409277 polymorphism and GG genotype of rs1561589 polymorphism had significantly lower total cholesterol (p = 0.001) and LDL cholesterol (p = 0.008) levels compared to all other groups of genotypes.ConclusionsOur study suggests that rs12409277 and rs1561589 polymorphism might have an influence on total and LDL cholesterol levels in adolescents. Larger studies should be performed in order to confirm our results.

scholarly journals Multifaceted Roles of Beige Fat in Energy Homeostasis Beyond UCP1

Endocrinology ◽  
2018 ◽  
Vol 159 (7) ◽  
pp. 2545-2553 ◽  
Author(s):  
Carlos Henrique Sponton ◽  
Shingo Kajimura
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Developmental Regulation ◽  
Brown Adipocytes ◽  
Adipose Tissue Depots ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Adipose Cells

Abstract Beige adipocytes are an inducible form of thermogenic adipose cells that emerge within the white adipose tissue in response to a variety of environmental stimuli, such as chronic cold acclimation. Similar to brown adipocytes that reside in brown adipose tissue depots, beige adipocytes are also thermogenic; however, beige adipocytes possess unique, distinguishing characteristics in their developmental regulation and biological function. This review highlights recent advances in our understanding of beige adipocytes, focusing on the diverse roles of beige fat in the regulation of energy homeostasis that are independent of the canonical thermogenic pathway via uncoupling protein 1.

scholarly journals Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis

2019 ◽  
Vol 116 (22) ◽  
pp. 10937-10942 ◽  
Author(s):  
Wenhai Sui ◽  
Hongshi Li ◽  
Yunlong Yang ◽  
Xu Jing ◽  
Fei Xue ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Atherosclerotic Plaque ◽  
Ldl Cholesterol ◽  
Uncoupling Protein ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cerebrovascular Diseases ◽  
Plaque Development ◽  
Brown Adipose

Mirabegron (Myrbetriq) is a β3-adrenoreceptor agonist approved for treating overactive bladder syndrome in human patients. This drug can activate brown adipose tissue (BAT) in adult humans and rodents through the β3-adrenoreceptor-mediated sympathetic activation. However, the effect of the mirabegron, approved by the US Food and Drug Administration, on atherosclerosis-related cardiovascular disease is unknown. Here, we show that the clinical dose of mirabegron-induced BAT activation and browning of white adipose tissue (WAT) exacerbate atherosclerotic plaque development. In apolipoprotein E−/− (ApoE−/−) and low-density lipoprotein (LDL) receptor−/− (Ldlr−/−) mice, oral administration of clinically relevant doses of mirabegron markedly accelerates atherosclerotic plaque growth and instability by a mechanism of increasing plasma levels of both LDL-cholesterol and very LDL-cholesterol remnants. Stimulation of atherosclerotic plaque development by mirabegron is dependent on thermogenesis-triggered lipolysis. Genetic deletion of the critical thermogenesis-dependent protein, uncoupling protein 1, completely abrogates the mirabegron-induced atherosclerosis. Together, our findings suggest that mirabegron may trigger cardiovascular and cerebrovascular diseases in patients who suffer from atherosclerosis.

Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization

1992 ◽  
Vol 103 (4) ◽  
pp. 931-942 ◽  
Author(s):  
B. Cousin ◽  
S. Cinti ◽  
M. Morroni ◽  
S. Raimbault ◽  
D. Ricquier ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Blot Hybridization ◽  
Morphological Characterization ◽  
Northern Blot Hybridization ◽  
Mitochondrial Uncoupling ◽  
Brown Adipocytes ◽  
Morphological Studies ◽  
Brown Adipose

Brown adipocytes are thermogenic cells which play an important role in energy balance. Their thermogenic activity is due to the presence of a mitochondrial uncoupling protein (UCP). Until recently, it was admitted that in rodents brown adipocytes were mainly located in classical brown adipose tissue (BAT). In the present study, we have investigated the presence of UCP protein or mRNA in white adipose tissue (WAT) of rats. Using polymerase chain reaction or Northern blot hybridization, UCP mRNA was detected in mesenteric, epidydimal, retroperitoneal, inguinal and particularly in periovarian adipose depots. The uncoupling protein was detected by Western blotting in mitochondria from periovarian adipose tissue. When rats were submitted to cold or to treatment with a beta-adrenoceptor agonist, UCP expression was increased in this tissue as in typical brown fat. Moreover, the expression was decreased in obese fa/fa rats compared to lean controls. Morphological studies showed that periovarian adipose tissue of rats kept at 24 degrees C contained cells with numerous typical BAT mitochondria with or without multilocular lipid droplets. Immunocytochemistry confirmed that multilocular cells expressed mitochondrial UCP. Furthermore, the number of brown adipocytes and the density of mitochondrial cristae increased in parallel with exposure to cold. These results demonstrate that adipocytes expressing UCP are present in adipose deposits considered as white fat. They suggest the existence of a continuum in rodents between BAT and WAT, and a great plasticity between adipose tissue phenotypes. The physiological importance of brown adipocytes in WAT and the regulation of UCP expression remain open questions.

Uncoupling protein 1 expression and high-fat diets

2011 ◽  
Vol 300 (1) ◽  
pp. R1-R8 ◽  
Author(s):  
Tobias Fromme ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Caloric Intake ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Thermoregulatory Function

Uncoupling protein 1 (Ucp1) is the key component of β-adrenergically controlled nonshivering thermogenesis in brown adipocytes. This process combusts stored and nutrient energy as heat. Cold exposure not only activates Ucp1-mediated thermogenesis to maintain normothermia but also results in adaptive thermogenesis, i.e., the recruitment of thermogenic capacity in brown adipose tissue. As a hallmark of adaptive thermogenesis, Ucp1 synthesis is increased proportionally to temperature and duration of exposure. Beyond this classical thermoregulatory function, it has been suggested that Ucp1-mediated thermogenesis can also be employed for metabolic thermogenesis to prevent the development of obesity. Accordingly, in times of excess caloric intake, one may expect a positive regulation of Ucp1. The general impression from an overview of the present literature is, indeed, an increased brown adipose tissue Ucp1 mRNA and protein content after feeding a high-fat diet (HFD) to mice and rats. The reported increases are very variable in magnitude, and the effect size seems to be independent of dietary fat content and duration of the feeding trial. In white adipose tissue depots Ucp1 mRNA is generally downregulated by HFD, indicating a decline in the number of interspersed brown adipocytes.

scholarly journals Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

2020 ◽  
Author(s):  
Xuemei Liu ◽  
Xiyu Feng ◽  
Chao Deng ◽  
Lu Liu ◽  
Yanping Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Olanzapine Treatment ◽  
Brown Adipose

Abstract Background: Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated. Methods: To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d .), simvastatin (3.0 mg/kg, t.i.d .), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks.Results: Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O+B. Conclusions: Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.

scholarly journals Novel Browning Agents, Mechanisms, and Therapeutic Potentials of Brown Adipose Tissue

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Umesh D. Wankhade ◽  
Michael Shen ◽  
Hariom Yadav ◽  
Keshari M. Thakali
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
Brown Adipocytes ◽  
Atp Production ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes

Nonshivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production in order to dissipate energy as heat. Because of its crucial role in regulating energy homeostasis, ongoing exploration of BAT has emphasized its therapeutic potential in addressing the global epidemics of obesity and diabetes. The recent appreciation that adult humans possess functional BAT strengthens this prospect. Furthermore, it has been identified that there are both classical brown adipocytes residing in dedicated BAT depots and “beige” adipocytes residing in white adipose tissue depots that can acquire BAT-like characteristics in response to environmental cues. This review aims to provide a brief overview of BAT research and summarize recent findings concerning the physiological, cellular, and developmental characteristics of brown adipocytes. In addition, some key genetic, molecular, and pharmacologic targets of BAT/Beige cells that have been reported to have therapeutic potential to combat obesity will be discussed.

scholarly journals Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation

2014 ◽  
Vol 307 (9) ◽  
pp. E793-E799 ◽  
Author(s):  
G. Andres Contreras ◽  
Yun-Hee Lee ◽  
Emilio P. Mottillo ◽  
James G. Granneman
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Main Site ◽  
Adipose Tissue Depots ◽  
Brown Adipose ◽  
White Fat

Brown adipocytes (BA) generate heat in response to sympathetic activation and are the main site of nonshivering thermogenesis in mammals. Although most BA are located in classic brown adipose tissue depots, BA are also abundant in the inguinal white adipose tissue (iWAT) before weaning. The number of BA is correlated with the density of sympathetic innervation in iWAT; however, the role of continuous sympathetic tone in the establishment and maintenance of BA in WAT has not been investigated. BA marker expression in iWAT was abundant in weaning mice but was greatly reduced by 8 wk of age. Nonetheless, BA phenotype could be rapidly reinstated by acute β3-adrenergic stimulation with CL-316,243 (CL). Genetic tagging of adipocytes with adiponectin-CreERT2 demonstrated that CL reinstates uncoupling protein 1 (UCP1) expression in adipocytes that were present before weaning. Chronic surgical denervation dramatically reduced the ability of CL to induce the expression of UCP1 and other BA markers in the tissue as a whole, and this loss of responsiveness was prevented by concurrent treatment with CL. These results indicate that ongoing sympathetic activity is critical to preserve the ability of iWAT fat cells to express a BA phenotype upon adrenergic stimulation.

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