Protective role of adipocyte hypoxia-inducible factor-2 in diet-induced obesity in mice

2014 ◽  
Vol 122 (03) ◽  
Author(s):  
R Garcia Martin ◽  
MF Rubín de Celis ◽  
A Ziogas ◽  
J Phieler ◽  
N Qin ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Protective Role ◽  
Diet Induced Obesity ◽  
Obesity In Mice

scholarly journals Nicotinamide Nucleotide Transhydrogenase (Nnt) is Related to Obesity in Mice

2020 ◽  
Vol 52 (12) ◽  
pp. 877-881
Author(s):  
Anne Kunath ◽  
John T. Heiker ◽  
Matthias Kern ◽  
Joanna Kosacka ◽  
Gesine Flehmig ◽  
...  
Keyword(s):  
Fat Mass ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Wild Type ◽  
Inner Mitochondrial Membrane ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Diet Induced Obesity ◽  
Highly Sensitive ◽  
Obesity In Mice

AbstractThe C57BL/6J (B6J) mouse strain has been widely used as a control strain for the study of metabolic diseases and diet induced obesity (DIO). B6J mice carry a spontaneous deletion mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7–11, resulting in expression of a truncated form of Nnt, an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this mutation in B6J mice is associated with epigonadal fat mass and altered sensitivity to diet induced obesity. To define the role of Nnt in the development of diet induced obesity, we generated first backcross (BC1) hybrids of wild type Nnt C57BL/6NTac and mutated Nnt C57BL/6JRj [(C57BL/6NTac×C57BL/6JRj)F1×C57BL/6NTac]. Body weight gain and specific fat-pad depot mass were measured in BC1 hybrids under high fat diet conditions. Both sexes of BC1 hybrids indicate that mice with Nnt wild type allele are highly sensitive to DIO and exhibit higher relative fat mass. In summary, our data indicate that the Nnt mutation in mice is associated with sensitivity to DIO and fat mass.

scholarly journals Protective Role of Hypoxia-Inducible Factor-2α against Ischemic Damage and Oxidative Stress in the Kidney

2007 ◽  
Vol 18 (4) ◽  
pp. 1218-1226 ◽  
Author(s):  
Ichiro Kojima ◽  
Tetsuhiro Tanaka ◽  
Reiko Inagi ◽  
Hideki Kato ◽  
Toshiharu Yamashita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hypoxia Inducible Factor ◽  
Protective Role ◽  
Ischemic Damage ◽  
And Oxidative Stress

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 Roxadustat (FG4592) alleviates Radiation-Induced Intestinal Injury by facilitating recovery of intestinal stem cell and reducing damage of intestinal epithelial cell

2020 ◽  
Author(s):  
Penglin Xia ◽  
Yajie Yang ◽  
Ruling Liu ◽  
Haibo Tang ◽  
Jicong Du ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Protective Role ◽  
Intestinal Injury ◽  
Intestinal Epithelial ◽  
Brdu Label ◽  
Retroperitoneal Tumors ◽  
Radiation Induced ◽  
Proliferation Potential

Abstract Background: Radiation induced-intestinal injury (RIII) is a common complication after radiation therapy in patients with pelvic, abdominal or retroperitoneal tumors. The mechanism of RIII includes radiation-induced death of intestinal epithelial cells (IECs) and damage of intestinal stem cells (ISCs), among which damage of ISCs is main cause. Most recently, hypoxia Inducible factor (HIF) has been found to have effect on maintaining stemness and promoting proliferation of ISCs, which suggests a protective role of HIF in the RIII. In this study, we investigated the effect of FG4592, a novel up-regulator of HIF, on the protection of RIII, and further researched its function on ISCs.Methods: With/without FG4592 treatment, the abdomen of mice was radiated at dose of 25Gy, and then the degree of intestinal injury was assessed by H&E staining and Brdu label. By intestinal organoid culture, the multiplication capacity and differentiation features of ISCs were detected. Besides, the effects of FG4592 on the radiated IECs were also evaluated by detecting cell viability, apoptosis, and proliferation potential.Results: FG4592 could effectively up-regulate the expression of HIF-1α and HIF-2α in vivo. An abdominal radiation of 25Gy established the RIII model of mice, by which FG4592 was verified to have protective effect on the intestine from radiation. Morphology and Brdu test of intestinal organoid showed that FG4592 could promote regeneration and differentiation in ISCs after radiation, which were mediated by up-regulating HIF-2 rather than HIF-1.Conclusion: FG4592, a novel up-regulator of HIF could remit RIII and promote regeneration and differentiation of ISCs after radiation, which were depend on HIF-2 rather than HIF-1.

scholarly journals Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sung-Soo Park ◽  
Yeon-Joo Lee ◽  
Hyuno Kang ◽  
Garam Yang ◽  
Eun Jeong Hong ◽  
...  
Keyword(s):  
Probiotic Bacterium ◽  
Protective Effects ◽  
Diet Induced Obesity ◽  
White Adipocytes ◽  
Lactobacillus Amylovorus ◽  
Obesity In Mice ◽  
Lactate Levels ◽  
Transcriptional Complex ◽  
And Function

AbstractBrowning of white adipose tissue (WAT) is currently considered a potential therapeutic strategy to treat diet-induced obesity. While some probiotics have protective effects against diet-induced obesity, the role of probiotics in adipose browning has not been explored. Here, we show that administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function, as well as the thermogenic gene program (increased Ucp1, PPARγ, and PGC-1α expression and decreased RIP140 expression), in subcutaneous inguinal WAT and also increased body temperature. Furthermore, LKU4 administration increased the interaction between PPARγ and PGC-1α through release of RIP140 to stimulate Ucp1 expression, thereby promoting browning of white adipocytes. In addition, lactate, the levels of which are elevated in plasma of HFD-fed mice following LKU4 administration, elicited the same effect on the interaction between PPARγ and PGC-1α in 3T3-L1 adipocytes, leading to a brown-like adipocyte phenotype that included enhanced Ucp1 expression, mitochondrial levels and function, and oxygen consumption rate. Together, these data reveal that LKU4 facilitates browning of white adipocytes through the PPARγ-PGC-1α transcriptional complex, at least in part by increasing lactate levels, leading to inhibition of diet-induced obesity.

scholarly journals Protective Role of Flavonoids Against Colonic Motor Dysfunctions Associated with High Fat Diet-Induced Obesity

2017 ◽  
Vol 152 (5) ◽  
pp. S828
Author(s):  
Daniela Gentile ◽  
Matteo Fornai ◽  
Rocchina Colucci ◽  
Carolina Pellegrini ◽  
Erika Tirotta ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Protective Role ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Colonic Motor

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.

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