Defective adaptive thermogenesis contributes to metabolic syndrome and liver steatosis in obese mice

2017 ◽  
Vol 131 (4) ◽  
pp. 285-296 ◽  
Author(s):  
Laurence Poekes ◽  
Vanessa Legry ◽  
Olivier Schakman ◽  
Christine Detrembleur ◽  
Anne Bol ◽  
...  

Defective adaptive high-fat diet (HFD)- and cold-induced thermogenesis, due to impaired sympathetic pathway in brown adipose tissue (BAT), contribute to metabolic syndrome and fatty liver. Improving thermogenic capacities by repeated cold exposure alleviates metabolic and hepatic complications of obesity.

2014 ◽  
Vol 221 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Gustavo W Fernandes ◽  
Cintia B Ueta ◽  
Tatiane L Fonseca ◽  
Cecilia H A Gouveia ◽  
Carmen L Lancellotti ◽  
...  

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.


1984 ◽  
Vol 247 (2) ◽  
pp. R290-R295 ◽  
Author(s):  
J. S. Fisler ◽  
T. Yoshida ◽  
G. A. Bray

Catecholamine turnover in response to fasting, cold exposure, and a high-fat diet has been measured in the Osborne-Mendel rat, which readily develops obesity when fed a high-fat diet, and the S 5B/P1 rat, which does not. We have tested the hypothesis that this difference in response to diet might be associated with altered rates of norepinephrine or epinephrine turnover. The endogenous norepinephrine concentration in interscapular brown adipose tissue was significantly greater in fasted S 5B/P1 rats than in fasted Osborne-Mendel rats. The fractional norepinephrine turnover rate in interscapular brown adipose tissue of fasted animals was also greater in the S 5B/P1 rat than in the Osborne-Mendel rat. Cold exposure increased the fractional norepinephrine turnover rate in interscapular brown adipose tissue for both strains of rats but increased the fractional norepinephrine turnover rate in the pancreas in only the Osborne-Mendel rats. The turnover of epinephrine and the adrenal concentration of this hormone were not different between the two strains. Normal and high-fat diets were fed to both strains; the Osborne-Mendel rats were pair fed the high-fat diet to prevent excess weight gain. Endogenous concentrations of norepinephrine in interscapular brown adipose tissue was increased by the high-fat diet; the increase was greater in S 5B/P1 rats. The high-fat diet resulted in increased norepinephrine turnover in interscapular brown adipose tissue of the S 5B/P1 rat but not the Osborne-Mendel rat.(ABSTRACT TRUNCATED AT 250 WORDS)


2019 ◽  
Author(s):  
Lulu Deng ◽  
Zihao Ou ◽  
Dongquan Huang ◽  
Chong Li ◽  
Zhi Lu ◽  
...  

Abstract Background The study aimed to investigate the differences of different Akkermansia muciniphila (A.muciniphila) genotypes on metabolic protective effects in mice with high-fat diet and explore possible mechanisms. Methods Male C57BL/6 mice were randomly divided into 6 groups, including high-fat diet (HFD)+ A.muciniphila I/II/PBS group, normal chow diet (NCD)+A.muciniphila I/ II /PBS group, respectively. Dietary intervention and A.muciniphila gavage were performed simultaneously. Blood glucose and lipid metabolism, brown adipose morphology and activities, and intestinal barrier function were examined after the mice were sacrificed. Results A.muciniphila gavage improved the impaired glucose tolerance, hyperlipidemia and liver steatosis in HFD mice, and that A.muciniphila II was not as effective as A.muciniphila I. This phenomenon might be because A.muciniphila I intervention significantly inhibited brown adipose tissue whitening and inflammation induced by HFD, by repairing the intestinal barrier and relieving endotoxemia. A.muciniphila II did not display the same results as A.muciniphila I in HFD mice, but had stronger effects in the NCD mice. Conclusions This study mainly reveals the distinct functions of different A.muciniphila genotypes on diet-induced obesity, suggesting that different A.muciniphila genotypes may play inequitable roles in pathological conditions through distinct action pathways.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1370
Author(s):  
Yufeng Shi ◽  
Honglei Zhai ◽  
Sharon John ◽  
Yi-Ting Shen ◽  
Yali Ran ◽  
...  

Obesity, a dysregulation of adipose tissue, is a major health risk factor associated with many diseases. Brown adipose tissue (BAT)-mediated thermogenesis can potentially regulate energy expenditure, making it an attractive therapeutic target to combat obesity. Here, we characterize the effects of cold exposure, thermoneutrality, and high-fat diet (HFD) feeding on mouse supraclavicular BAT (scBAT) morphology and BAT-associated gene expression compared to other adipose depots, including the interscapular BAT (iBAT). scBAT was as sensitive to cold induced thermogenesis as iBAT and showed reduced thermogenic effect under thermoneutrality. While both scBAT and iBAT are sensitive to cold, the expression of genes involved in nutrient processing is different. The scBAT also showed less depot weight gain and more single-lipid adipocytes, while the expression of BAT thermogenic genes, such as Ucp1, remained similar or increased more under our HFD feeding regime at ambient and thermoneutral temperatures than iBAT. Together, these findings show that, in addition to its anatomical resemblance to human scBAT, mouse scBAT possesses thermogenic features distinct from those of other adipose depots. Lastly, this study also characterizes a previously unknown mouse deep neck BAT (dnBAT) depot that exhibits similar thermogenic characteristics as scBAT under cold exposure and thermoneutrality.


2012 ◽  
Vol 1 ◽  
Author(s):  
Takahiko Fujikawa ◽  
Tetsuya Hirata ◽  
Shingo Hosoo ◽  
Kenji Nakajima ◽  
Atsunori Wada ◽  
...  

AbstractEucommia leaves (Eucommia ulmoides Oliver) contain chlorogenic acid (a caffeic acid derivative) and geniposidic acid and asperuloside (ASP), iridoid glucosides used in beverages. We used a metabolic syndrome rat model, produced by feeding a 35 % high-fat diet (HFD), to examine potential anti-obesity and anti-metabolic syndrome effects and mechanisms of chronic administration of ASP. These effects were compared with Eucommia leaf extract (ELE), the positive control, which exhibits anti-obesity effects. A total of six rats were studied for 3 months in five groups. ASP suppressed body weight, visceral fat weight, food intake and circulating levels of glucose, insulin and lipids, and increased the plasma adiponectin level in rats on a HFD. These effects are similar to those of ELE, except for the influence on the plasma glucose level. RT–PCR studies showed that ASP (like ELE with known anti-obesity effects) diminished isocitrate dehydrogenase 3α, NADH dehydrogenase flavoprotein 1 (Comp I) mRNA and fatty acid synthase levels (white adipose tissue), increased carnitine palmitoyltransferase 1α and acyl-CoA dehydrogenase, very-long-chain mRNA levels (liver), and increased Glut4, citrate synthase, isocitrate dehydrogenase 3α, succinyl CoA synthase, peroxisomal 3-ketoacyl-CoA thiolase, dihydrolipoamide succinyl transferase and succinate dehydrogenase mRNA levels (skeletal muscle) under HFD conditions. Interestingly, ASP administration resulted in significantly increased mRNA levels of uncoupling protein 1 (UCP1) in the brown adipose tissue of HFD-fed rats; ELE did not affect the expression of UCP1. The increased expression of UCP1 may be negated by many ingredients other than ASP in the ELE. These findings suggest that chronic administration of ASP stimulates anti-obesity and anti-metabolic syndrome activity in HFD-fed rats across several organs, similar to ELE administration; thus, ASP may be an important ingredient of ELE.


Theranostics ◽  
2020 ◽  
Vol 10 (18) ◽  
pp. 8197-8210 ◽  
Author(s):  
Xueying Zhou ◽  
Zhelong Li ◽  
Meihao Qi ◽  
Ping Zhao ◽  
Yunyou Duan ◽  
...  

2021 ◽  
pp. 1-11
Author(s):  
Lissette Duarte ◽  
Javier Quezada ◽  
Luisa A. Ramirez ◽  
Karla Vasquez ◽  
Juan F. Orellana ◽  
...  

BACKGROUND: Polyphenols intake increases the function of brown adipose tissue (BAT), stimulating energy expenditure (EE). Calafate (Berberis microphylla) is a polyphenol-rich Chilean native fruit. OBJECTIVE: To analyse the effect of a treatment with a Calafate extract in the thermogenic activity of mice adipose tissues. METHODS: Forty adult C57BL/6J male mice were subdivided into four groups (n=10 each): control diet, control+Calafate (extract: 50mg total polyphenols/kg weight), high-fat diet (HF) and HF+Calafate. RESULTS: Calafate prevented the increase in body weight and the decrease EE induced by HF. In BAT, Ucp-1 transcript was influenced by the interaction between diet and Calafate (p<0.01), Pparα showed the same expression pattern as Ucp-1 and both, diet (p<0.01) and Calafate (p<0.05), induced significant effects in Sirt1. In inguinal adipose tissue, Pgc1α, Pparα, Prdm16, Sirt1, and Dio2 transcripts presented a decreased expression caused by HF, that was reversed by Calafate. In BAT, an effect of diet (p<0.05) and an interaction between diet and Calafate (p<0.01) was observed in UCP-1 protein levels. CONCLUSIONS: A treatment with Calafate drives less weight gain in mice fed with HF, and reverses the effects generated by it on the expression of thermogenic and browning markers.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 804
Author(s):  
Adéla Kábelová ◽  
Hana Malínská ◽  
Irena Marková ◽  
Olena Oliyarnyk ◽  
Blanka Chylíková ◽  
...  

Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet–ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet–control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Tomoyasu Kamiya ◽  
Mayu Sameshima-Kamiya ◽  
Rika Nagamine ◽  
Masahito Tsubata ◽  
Motoya Ikeguchi ◽  
...  

Kudzu, a leguminous plant, has long been used in folk medicine. In particular, its flowers are used in Japanese and Chinese folk medicine for treating hangovers. We focused on the flower of Kudzu (Puerariae thomsonii), and we previously reported the antiobesity effect ofPuerariae thomsoniiflower extract (PFE) in humans. In this study, we conducted an animal study to investigate the effect of PFE on visceral fat and hepatic lipid levels in mice with diet-induced obesity. In addition, we focused on gene expression profiles to investigate the antiobesity mechanism of PFE. Male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with 5% PFE for 14 days. PFE supplementation significantly reduced body weight and white adipose tissue (WAT) weight. Moreover, in the histological analysis, PFE supplementation improved fatty liver. Hepatic reverse transcription-polymerase chain reaction revealed that PFE supplementation downregulated acetyl-CoA carboxylase expression. For adipose tissue, the expressions of hormone-sensitive lipase in WAT and uncoupling protein 1 in brown adipose tissue (BAT) were significantly upregulated. These results suggest that PFE exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice through suppressing lipogenesis in the liver, stimulating lipolysis in WAT, and promoting thermogenesis in BAT.


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