scholarly journals L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice

2021 ◽  
Author(s):  
Wan-Qiu Peng ◽  
Gang Xiao ◽  
Bai-Yu Li ◽  
Ying-Ying Guo ◽  
Liang Guo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Intraperitoneal Administration ◽  
Dna Demethylation ◽  
Active Dna Demethylation ◽  
Diet Induced Obesity ◽  
Elevated Expression ◽  
Obesity In Mice

L-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with L-Theanine(100mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1 and other thermogenic genes. Meanwhile, administration of the mice with L-Theanine increased energy expenditure. In vitro studies indicated that L-Theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of L-Theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. L-Theanine treatment enhanced AMPKα phosphorylation both in adipocytes and in iWAT. Knockdown of AMPKα ablolished L-Theanine-induced upregulation of Prdm16 and adipocytes browning. L-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for L-Theanine-induced increase of α-KG and DNA demethylation on Prdm16 promoter. Moreover, intraperitoneal administration with L-Theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol and free fatty acid in the high fat diet-fed mice. Our results suggest a potential role of L-Theanine in combating diet-induced obesity in mice, which may involve L-Theanine-induced browning of white adipose tissue.

scholarly journals L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice

2021 ◽  
Author(s):  
Wan-Qiu Peng ◽  
Gang Xiao ◽  
Bai-Yu Li ◽  
Ying-Ying Guo ◽  
Liang Guo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Intraperitoneal Administration ◽  
Dna Demethylation ◽  
Active Dna Demethylation ◽  
Diet Induced Obesity ◽  
Elevated Expression ◽  
Obesity In Mice

L-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with L-Theanine(100mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1 and other thermogenic genes. Meanwhile, administration of the mice with L-Theanine increased energy expenditure. In vitro studies indicated that L-Theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of L-Theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. L-Theanine treatment enhanced AMPKα phosphorylation both in adipocytes and in iWAT. Knockdown of AMPKα ablolished L-Theanine-induced upregulation of Prdm16 and adipocytes browning. L-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for L-Theanine-induced increase of α-KG and DNA demethylation on Prdm16 promoter. Moreover, intraperitoneal administration with L-Theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol and free fatty acid in the high fat diet-fed mice. Our results suggest a potential role of L-Theanine in combating diet-induced obesity in mice, which may involve L-Theanine-induced browning of white adipose tissue.

L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice

Diabetes ◽  
2021 ◽  
pp. db201210
Author(s):  
Wan-Qiu Peng ◽  
Gang Xiao ◽  
Bai-Yu Li ◽  
Ying-Ying Guo ◽  
Liang Guo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Diet Induced Obesity ◽  
Obesity In Mice

scholarly journals Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression

2020 ◽  
Vol 6 (49) ◽  
pp. eabc6250
Author(s):  
Andréa Livia Rocha ◽  
Tanes Imamura de Lima ◽  
Gerson Profeta de Souza ◽  
Renan Oliveira Corrêa ◽  
Danilo Lopes Ferrucci ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Mirna Expression ◽  
Oxidative Metabolism ◽  
Target Genes ◽  
Cell Models ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Obesity In Mice

MicroRNAs (miRNAs) have been implicated in oxidative metabolism and brown/beige adipocyte identity. Here, we tested whether widespread changes in miRNA expression promoted by treatment with the small-molecule enoxacin cause browning and prevent obesity. Enoxacin mitigated diet-induced obesity in mice, and this was associated with increased energy expenditure. Consistently, subcutaneous white and brown adipose tissues and skeletal muscle of enoxacin-treated mice had higher levels of markers associated with thermogenesis and oxidative metabolism. These effects were cell autonomous since they were recapitulated in vitro in murine and human cell models. In preadipocytes, enoxacin led to a reduction of miR-34a-5p expression and up-regulation of its target genes (e.g., Fgfr1, Klb, and Sirt1), thus increasing FGF21 signaling and promoting beige adipogenesis. Our data demonstrate that enoxacin counteracts obesity by promoting thermogenic signaling and inducing oxidative metabolism in adipose tissue and skeletal muscle in a mechanism that involves, at least in part, miRNA-mediated regulation.

scholarly journals RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2014 ◽  
Vol 224 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Xiao-Bing Cui ◽  
Jun-Na Luan ◽  
Jianping Ye ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Tolerance Test ◽  
High Fat ◽  
Diet Induced Obesity

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32−/− (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32−/− mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32−/− induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice

2007 ◽  
Vol 292 (4) ◽  
pp. E1079-E1086 ◽  
Author(s):  
John W. Bullen ◽  
Susann Bluher ◽  
Theodoros Kelesidis ◽  
Christos S. Mantzoros
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Adiponectin Mrna ◽  
Obesity In Mice ◽  
Fat Feeding

Adiponectin and its receptors play an important role in energy homeostasis and insulin resistance, but their regulation remains to be fully elucidated. We hypothesized that high-fat diet would decrease adiponectin but increase adiponectin receptor (AdipoR1 and AdipoR2) expression in diet-induced obesity (DIO)-prone C57BL/6J and DIO-resistant A/J mice. We found that circulating adiponectin and adiponectin expression in white adipose tissue are higher at baseline in C57BL/6J mice compared with A/J mice. Circulating adiponectin increases at 10 wk but decreases at 18 wk in response to advancing age and high-fat feeding. However, adiponectin levels corrected for visceral fat mass and adiponectin mRNA expression in WAT are affected by high-fat feeding only, with both being decreased after 10 wk in C57BL/6J mice. Muscle AdipoR1 expression in both C57BL/6J and A/J mice and liver adipoR1 expression in C57BL/6J mice increase at 18 wk of age. High-fat feeding increases both AdipoR1 and AdipoR2 expression in liver in both strains of mice and increases muscle AdipoR1 expression in C57BL/6J mice after 18 wk. Thus advanced age and high-fat feeding, both of which are factors that predispose humans to obesity and insulin resistance, are associated with decreasing adiponectin and increasing AdipoR1 and/or AdipoR2 levels.

Neuromedin U has a physiological role in the regulation of food intake and partially mediates the effects of leptin

2005 ◽  
Vol 289 (2) ◽  
pp. E301-E305 ◽  
Author(s):  
Preeti H. Jethwa ◽  
Caroline J. Small ◽  
Kirsty L. Smith ◽  
Asha Seth ◽  
Sarah J. Darch ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Energy Expenditure ◽  
Immunoglobulin G ◽  
Intraperitoneal Administration ◽  
Physiological Role ◽  
Dark Phase ◽  
Fasted Rats

Intracerebroventricular (ICV) administration of Neuromedin U (NMU), a hypothalamic neuropeptide, or leptin, an adipostat hormone released from adipose tissue, reduces food intake and increases energy expenditure. Leptin stimulates the release of NMU in vitro, and NMU expression is reduced in models of low or absent leptin. We investigated the role of NMU in mediating leptin-induced satiety. ICV administration of anti-NMU immunoglobulin G (IgG) (5 nmol) to satiated rats significantly increased food intake 4 h after injection, an effect seen for ≤8 h after injection. ICV administration of NMU (1 nmol) to fasted rats reduced food intake 1 h after injection compared with control, an effect attenuated by pretreatment with anti-NMU IgG. ICV administration of leptin (0.625 nmol) reduced 24-h food intake. This was partially attenuated by the administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 22.5 ± 2.0 g; leptin, 13.7 ± 2.3 g ( P < 0.005 vs. vehicle), leptin/NMU IgG, 19.4 ± 1.3 g ( P < 0.05 vs. leptin)]. Intraperitoneal administration of leptin (1.1 mg/kg body wt) reduced 24-h food intake. This was partially attenuated by ICV administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 31.4 ± 4.9 g; leptin, 20.8 ± 2.6 g ( P < 0.01 vs. vehicle); leptin/NMU IgG, 28.7 ± 1.1 g ( P < 0.01 vs. leptin)]. These results suggest that NMU plays a physiological role in the regulation of appetite and partially mediates the leptin-induced satiety.

scholarly journals Cinnamaldehyde Ameliorates Diet-Induced Obesity in Mice by Inducing Browning of White Adipose Tissue

2017 ◽  
Vol 42 (4) ◽  
pp. 1514-1525 ◽  
Author(s):  
Jiacheng Zuo ◽  
Dandan Zhao ◽  
Na Yu ◽  
Xin Fang ◽  
Qianqian Mu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Health Concern ◽  
Standard Diet ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diet Induced Obesity ◽  
Obesity In Mice ◽  
Pr Domain

Background/Aims: Obesity has become a major health concern with few effective medications. Cinnamaldehyde (CA) has been reported to exhibit anti-diabetic and anti-inflammatory properties. However, whether CA shows anti-obesity activity remains unknown. Therefore, the present study aimed to investigate the potential anti-obesity effects of CA on mice fed a high-fat diet (HFD) and to explore the possible mechanisms involved. Methods: Male C57BL/6J mice fed an HFD for 12 weeks were supplemented with CA (40 mg/kg/day) via gavage for an additional 8 weeks. Mice fed a standard diet were used as normal controls. Results: The results revealed that CA treatment decreased body weight, fat mass, food intake, and serum lipid, free fatty acid and leptin levels. CA administration also improved insulin sensitivity in HFD-induced obese mice. Additionally, CA inhibited the hypertrophy of adipose tissue and induced browning of white adipose tissue. Uncoupling protein 1 (UCP1) was expressed in white adipose tissue after the oral administration of CA. Furthermore, CA enhanced the expression of the peroxisome proliferator-activated receptor γ (PPARγ), PR domain-containing 16 (PRDM16) and PPARγ coactivator 1α (PGC-1α) proteins in both brown and white adipose tissues. Conclusions: The results suggest that CA exhibits therapeutic potency against obesity by inducing the browning of white adipose tissue in HFD-fed mice.

Resistance to Diet-Induced Obesity in Mice Lacking OPA1 in Adipose Tissue Occurs Independently of Fat-Derived FGF-21 and BAT Function

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 276-LB ◽  
Author(s):  
RENATA PEREIRA ◽  
ANGELA C. OLVERA ◽  
ALEX A. MARTI ◽  
RANA HEWEZI ◽  
WILLIAM A. BUI TRAN ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Diet Induced Obesity ◽  
Obesity In Mice

scholarly journals Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Dasol Kim ◽  
Hui-Yun Hwang ◽  
Eun Sun Ji ◽  
Jin Young Kim ◽  
Jong Shin Yoo ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Elongation Factor ◽  
Dependent Manner ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Autophagy Induction ◽  
Transcription Factor Eb ◽  
Mitochondrial Elongation

AbstractDisorders of autophagy, a key regulator of cellular homeostasis, cause a number of human diseases. Due to the role of autophagy in metabolic dysregulation, there is a need to identify autophagy regulators as therapeutic targets. To address this need, we conducted an autophagy phenotype-based screen and identified the natural compound kaempferide (Kaem) as an autophagy enhancer. Kaem promoted autophagy through translocation of transcription factor EB (TFEB) without MTOR perturbation, suggesting it is safe for administration. Moreover, Kaem accelerated lipid droplet degradation in a lysosomal activity-dependent manner in vitro and ameliorated metabolic dysregulation in a diet-induced obesity mouse model. To elucidate the mechanism underlying Kaem’s biological activity, the target protein was identified via combined drug affinity responsive target stability and LC–MS/MS analyses. Kaem directly interacted with the mitochondrial elongation factor TUFM, and TUFM absence reversed Kaem-induced autophagy and lipid degradation. Kaem also induced mitochondrial reactive oxygen species (mtROS) to sequentially promote lysosomal Ca2+ efflux, TFEB translocation and autophagy induction, suggesting a role of TUFM in mtROS regulation. Collectively, these results demonstrate that Kaem is a potential therapeutic candidate/chemical tool for treating metabolic dysregulation and reveal a role for TUFM in autophagy for metabolic regulation with lipid overload.

scholarly journals Effects of stem cells from inducible brown adipose tissue on diet-induced obesity in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Enrique Calvo ◽  
Noelia Keiran ◽  
Catalina Núñez-Roa ◽  
Elsa Maymó-Masip ◽  
Miriam Ejarque ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Therapeutic Option ◽  
Metabolic Activation ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Obesity In Mice ◽  
Treatment Of Obesity ◽  
Visceral Adipose

AbstractAdipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

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