• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.645-650
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• 2019

Brown adipocytes have an important role in the regulation of energy balance through uncoupling protein-1 (UCP-1)-mediated nonshivering thermogenesis. Although brown adipocytes have been highlighted as a new therapeutic target for the treatment of metabolic diseases, such as obesity and type II diabetes in adult humans, the molecular mechanism underlying brown adipogenesis is not fully understood. We recently found that protein tyrosine phosphatase receptor type B (PTPRB) expression dramatically decreased during brown adipogenic differentiation. In this study, we investigated the functional roles of PTPRB and its regulatory mechanism during brown adipocyte differentiation. Ectopic expression of PTPRB led to a reduced brown adipocyte differentiation by suppressing the tyrosine phosphorylation of VEGFR2, whereas a catalytic inactive PTPRB mutant showed no effects on differentiation and phosphorylation. Consistently, the expression of brown adipocyte-related genes, such as UCP-1, $PGC-1{\alpha}$, PRDM16, $PPAR-{\gamma}$, and CIDEA, were significantly inhibited by PTPRB overexpression. Overall, these results suggest that PTPRB functions as a negative regulator of brown adipocyte differentiation through its phosphatase activity-dependent mechanism and may be used as a target protein for the regulation of obesity and type II diabetes.

• Animal Bioscience
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• v.35 no.7
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• pp.1010-1020
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• 2022

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW^0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW^0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

• Korean Journal of Exercise Nutrition
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• v.13 no.2
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• pp.93-100
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• 2009

This study was conducted to investigate the effect of exercise training on blood and metabolic variances and genes expressions in hyperlipidemic rats. Three weeks-old male rats were randomly assigned into chow (n=7), high-fat diet (HF, n=7) and HF+exercise (HF+EX, n=7) groups. Exercise training consisted of the treadmill running 5 times per week during 8 weeks (0% grade, 30 min/time for first 4 weeks and 0% grade, 60 min/time the other 4weeks). The levels of triglyceride and total -cholesterol were increased in HF diet compared with chow group, and recovered to level of chow group by exercise training. Plasma glucose and insulin concentrations increased by 40 and 50%, respectively in HF diet compared with chow diet group, and these increases returned to the level of chow group by exercise training (p<.05). Body weight and abdominal fat mass were increased by high-fat diet compared with chow diet, and recovered to level of chow group by exercise training. Long-chain fatty acid oxidation rate and AMPK protein expression was not changed by HF diet, but increased by exercise training compared with high-fat diet (p<.05). UCP3 protein expression was not changed by either high-fat diet or exercise training compared with chow group. There was high correlation between plasma triglyceride and total cholesterol concentrations(p<.01). Plasma triglyceride or total cholesterol level showed correlation with following factors; plasma insulin and glucose levels, body weight, abdominal fat weight, UCP3 protein expression and long-chain fatty acid oxidation rate. These results showed that exercise training on the treadmill recovered hyperlipidemia, hyperglycemia and hyperinsulinemia induced by high-fat diet for 8 weeks. These exercise effects may be related with decreased body weight and abdominal fat mass, and increased long-chain fatty acid oxidation rate.

• Journal of Nutrition and Health
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• v.57 no.2
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• pp.171-184
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• 2024

Purpose: Although activating thermogenic adipocytes is a promising strategy to reduce the risk of obesity and related metabolic disorders, emerging evidence suggests that it is difficult to induce adipocyte thermogenesis in obesity. Therefore, this study aimed to investigate the regulation of adipocyte thermogenesis in diet-induced obesity. Methods: Adipose progenitor cells were isolated from the white and brown adipose tissues of control diet (CD) or high-fat diet (HFD) fed mice, and fully differentiated white and brown adipocytes were treated with β-agonists or 18-carbon fatty acids for β-adrenergic activation or peroxisome proliferator-activated receptor (PPAR) activation. Results: Compared to the CD-fed mice, the expression of uncoupling protein 1 (Ucp1) was lower in the white adipose tissue of the HFD-fed mice; however, this was not observed in the brown adipose tissue. The expression of peroxisome proliferator-activated receptor gamma (Pparg) was lower in the brown adipose progenitor cells isolated from HFD-fed mice than in those isolated from the CD-fed mice. Norepinephrine (NE) treatment exerted lesser effect on peroxisome proliferator-activated receptor-γ coactivator (Pgc1a) upregulation in white adipocytes derived from HFD-fed mice than those derived from CD-fed mice. Regardless which 18-carbon fatty acids were treated, the expression levels of thermogenic genes including Ucp1, Pgc1a, and positive regulatory domain zinc finger region protein 16 (Prdm16) were higher in the white adipocytes derived from HFD-fed mice. Oleic acid (OLA) and γ-linolenic acid (GLA) upregulated Pgc1a expression in white adipocytes derived from HFD-fed mice. Brown adipocytes derived from HFD-fed mice had higher expression levels of Pgc1a and Prdm16 compared to their counterparts. Conclusion: These results indicate that diet-induced obesity may downregulate brown adipogenesis and NE-induced thermogenesis in white adipocytes. Also, HFD feeding may induce thermogenic gene expression in white and brown primary adipocytes, and OLA and GLA could augment the expression levels.

• Nutritional Sciences
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• v.6 no.3
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• pp.148-154
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• 2003

Although various raw plant materials have been demonstrated to exert anti-obesity effects to a greater or lesser extent in both humans and animals when they are used to supplement the diet, it has not been shown extensively that they influence adipocyte cell differentiation involving lipid metabolic gene expressions. Using a well-established 3T3-L1 preadipocyte differentiation system, we decided to look into molecular and cellular event occurring during adipocyte differentiation when raw plant materials aye included in the process, in an effort to demonstrate the potential use of a screening system to define the functions of traditionally well-known materials. To these ends, the effects of ethanol (EtOH) or EtOH/distilled water (DW) extracts of Wax Gourd were examined using cytochemical and molecular analyses to determine whether components of the extracts modulate adipocyte differentiation of 3T3-Ll preadipocytes in vitro. The cytochemical results demonstrated that EtOH or EtOH/DW extracts did not affect lipid accumulation and cell proliferation, although the degree of lipid accumulation was influenced slightly depending on the extract. EtOH extract was highly effective in apoptotic induction during differentiation of 3T3-Ll preadipocytes (p<0.05). Reverse transcription-polymerase chain reaction (RT-PCR) analysis of lipoprotein lipase (LPL), Uncoupling protein (Ucp) 2, 3 and 4 also showed that while LPL expression was not influenced, Ucp2, 3 and 4 were up regulated in the EtOH extract-treated group and down regulated in the EtOH/DW extract-treated group. These changes in gene expressions suggest that the components in different fractions of Wax Gourd extracts may modulate lipid metabolism by either direct or indirect action. Taking these results together, it was concluded that molecular and cellular analyses of adipocyte differentiation involving lipid metabolic genes should facilitate understanding of cellular events occurring during adipocyte differentiation. Furthermore, the experimental scheme and analytical methods used in this study should provide a screening system for the functional study of raw plant materials in obesity research.

• Nutrition Research and Practice
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• v.16 no.1
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• pp.14-32
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• 2022

BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

• BMB Reports
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• v.53 no.3
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• pp.142-147
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• 2020

Lipid accumulation in white adipose tissue is the key contributor to the obesity and orchestrates numerous metabolic health problems such as type 2 diabetes, hypertension, atherosclerosis, and cancer. Nonetheless, the prevention and treatment of obesity are still inadequate. Recently, scientists found that brown adipose tissue (BAT) in adult humans has functions that are diametrically opposite to those of white adipose tissue and that BAT holds promise for a new strategy to counteract obesity. In this study, we evaluated the potential of sinapic acid (SA) to promote the thermogenic program and lipolysis in BAT. SA treatment of brown adipocytes induced the expression of brown-adipocyte activation-related genes such as Ucp1, Pgc-1α, and Prdm16. Furthermore, structural analysis and western blot revealed that SA upregulates protein kinase A (PKA) phosphorylation with competitive inhibition by a pan-PKA inhibitor, H89. SA binds to the adenosine triphosphate (ATP) site on the PKA catalytic subunit where H89 binds specifically. PKA-cat-α1 gene-silencing experiments confirmed that SA activates the thermogenic program via a mechanism involving PKA and cyclic AMP response element-binding protein (CREB) signaling. Moreover, SA treatment promoted lipolysis via a PKA/p38-mediated pathway. Our findings may allow us to open a new avenue of strategies against obesity and need further investigation.

• Food Science and Biotechnology
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• v.17 no.2
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• pp.336-342
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• 2008

The aim of the present study was to assess the anti-obesity effects of fermented kochujang supplement in C57BL/6J mice. Thirty mice were divided into 3 groups; normal diet control group (ND), high fat diet control group (HD), and high fat diet plus kochujang supplemented group (HDK). Results were as follows: 1. Fennented kochujang supplement in high fat diet decreased body weight and epidydimal and back fat weight compared to non-supplement in HD group. 2. Lipid content and blood glucose level were lower in HDK group than HD group. 3. Fermented kochujang supplement increased mRNA level of lipolytic genes such as acyl-CoA synthetase (ACS), carnitine palmitoyltransferase-1 (CPT-1), and uncoupling proteins-1 (UCP-1) expression, whereas decreased mRNA level of adipogenic genes such as acetyl CoA carboxylase (ACC) expression. These findings suggest that fermented kochujang supplement in high fat diet normalized body weight, epididymal and back fat weight, lipid content, and blood glucose levels through controlling lipid metabolism and provides basic information on the control of obesity.

• Journal of Pharmacopuncture
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• v.12 no.2
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• pp.13-20
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• 2009

In this study, the effects of Ganoderma lucidum (GL) on fat metabolism were performed in 3T3-L1 adipocytes. The effects of GL on 3T3-L1 preadipocytes differentiation were also examined. Our results showed that GL decreased the TG content by ORO staining. To elucidate the mechanism of the effects of GL on lowering TG content in 3T3-L1 adipocytes, we examined whether GL modulate the expressions of transcription factors and adipokines related to control of energy expenditure process because adipokines regulate adipocyte mass and increased expenditure may consume much TG in adipocytes. As a result, the expression of C/$EBP{\beta}$, C/$EBP{\delta}$, C/$EBP{\alpha}$, and $PPAR{\gamma}$, genes, which induce the adipose differentiation and adipose-specific FAS, aP2, and adipsin genes, which compose fat formation were decreased. In addition, GL increased the expression of leptin, UCP2, adiponectin in 3T3-L1 adipocytes, resulting in energy homeostasis. In conclusion, GL could regulate transcript factor related to induction of adipose differentiation and control TG content by up-regulation of adipokines related to fat burn.

• Journal of Nutrition and Health
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• v.55 no.4
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• pp.462-475
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• 2022

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.