scholarly journals Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue

2018 ◽  
Vol 9 ◽  
Author(s):  
Natalia de las Heras ◽  
Mercedes Klett-Mingo ◽  
Sandra Ballesteros ◽  
Beatriz Martín-Fernández ◽  
Óscar Escribano ◽  
...  
Author(s):  
Soren Z. Coulson ◽  
Cayleih E. Robertson ◽  
Sajeni Mahalingam ◽  
Grant B. McClelland

High altitude environments challenge small mammals with persistent low ambient temperatures that require high rates of aerobic heat production in face of low O2 availability. An important component of thermogenic capacity in rodents is non-shivering thermogenesis (NST) mediated by uncoupled mitochondrial respiration in brown adipose tissue (BAT). NST is plastic, and capacity for heat production increases with cold acclimation. However, in lowland native rodents, hypoxia inhibits NST in BAT. We hypothesize that highland deer mice (Peromyscus maniculatus) overcome the hypoxic inhibition of NST through changes in BAT mitochondrial function. We tested this hypothesis using lab born and raised highland and lowland deer mice, and a lowland congeneric (P. leucopus), acclimated to either warm normoxia (25°C, 760 mmHg) or cold hypoxia (5°C, 430 mmHg). We determined the effects of acclimation and ancestry on whole-animal rates of NST, the mass of interscapular BAT (iBAT), and uncoupling protein (UCP)-1 protein expression. To identify changes in mitochondrial function, we conducted high-resolution respirometry on isolated iBAT mitochondria using substrates and inhibitors targeted to UCP-1. We found that rates of NST increased with cold hypoxia acclimation but only in highland deer mice. There was no effect of cold hypoxia acclimation on iBAT mass in any group, but highland deer mice showed increases in UCP-1 expression and UCP-1 stimulated mitochondrial respiration in response to these stressors. Our results suggest that highland deer mice have evolved to increase the capacity for NST in response to chronic cold hypoxia, driven in part by changes in iBAT mitochondrial function.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ryutaro Ikegami ◽  
Ippei Shimizu ◽  
Takeshi Sato ◽  
Shuang Jiao ◽  
Yohko Yoshida ◽  
...  

Accumulating evidence suggests that adult humans possess active brown adipose tissue (BAT) that may contribute significantly to systemic metabolism because of its high energy consumption capacity. Recently, we demonstrated that metabolic stress induced BAT hypoxia and impaired mitochondrial function, leading to the development of BAT “whitening” and systemic metabolic dysfunction in murine obese models. Various neurotransmitters are known to be involved in the maintenance of BAT homeostasis. Among them, the gamma-aminobutyric acid (GABA) signaling in the central nervous system is well accepted to have anti-obesity effects through the activation of the sympathetic nervous system. Here we show the previously unknown role of peripheral GABA signaling in the development of systemic metabolic dysfunction in obesity. We generated an obese model by imposing a high fat/high sucrose (HFHS) diet on C57BL/6NCr mice. Mass spectrometry analysis demonstrated a significant increase in GABA level in BAT of the dietary obese model. Addition of GABA into drinking water induced BAT whitening, reduced the thermogenic response upon cold tolerance test, and promoted systemic metabolic dysfunction in the obese mice. Mitochondrial calcium is important for the maintenance of mitochondrial homeostasis, whereas calcium overload is reported to inhibit mitochondrial function. Treatment of BAT cells with GABA markedly increased mitochondrial calcium level, promoted the production of reactive oxygen species (ROS), and inhibited mitochondrial respiration. These results indicate that peripheral GABA contributes to the development of systemic metabolic dysfunction by inhibiting BAT function in obesity. The inhibition of peripheral GABA signaling would become a new therapeutic target for obesity and diabetes.


2011 ◽  
Vol 107 (2) ◽  
pp. 170-178 ◽  
Author(s):  
David Pajuelo ◽  
Helena Quesada ◽  
Sabina Díaz ◽  
Anabel Fernández-Iglesias ◽  
Anna Arola-Arnal ◽  
...  

The present study aims to determine the effects of grape seed proanthocyanidin extract (GSPE) on brown adipose tissue (BAT) mitochondrial function in a state of obesity induced by diet. Wistar male rats were fed with a cafeteria diet (Cd) for 4 months; during the last 21 d, two groups were treated with doses of 25 and 50 mg GSPE/kg body weight. In the BAT, enzymatic activities of citrate synthase, cytochrome c oxidase (COX) and ATPase were determined and gene expression was analysed by real-time PCR. The mitochondrial function of BAT was determined in fresh mitochondria by high-resolution respirometry using both pyruvate and carnitine–palmitoyl-CoA as substrates. The results show that the Cd causes an important decrease in the gene expression of sirtuin 1, nuclear respiratory factor 1, isocitrate dehydrogenase 3γ and COX5α and, what is more telling, decreases the levels of mitochondrial respiration both with pyruvate and canitine–palmitoyl-CoA. Most of these parameters, which are indicative of mitochondrial dysfunction due to diet-induced obesity, are improved by chronic supplementation of GSPE. The beneficial effects caused by the administration of GSPE are exhibited as a protection against weight gain, in spite of the Cd the rats were fed. These data indicate that chronic consumption of a moderate dose of GSPE can correct an energy imbalance in a situation of diet-induced obesity, thereby improving the mitochondrial function and thermogenic capacity of the BAT.


Steroids ◽  
2011 ◽  
Vol 76 (10-11) ◽  
pp. 1051-1056 ◽  
Author(s):  
Antònia Nadal-Casellas ◽  
Ana M. Proenza ◽  
Isabel Lladó ◽  
Magdalena Gianotti

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Yuan ◽  
Juan Li ◽  
Wei-Gang Zhao ◽  
Wei Sun ◽  
Shuai-Nan Liu ◽  
...  

Abstract Background To investigate effects of metformin on the regulation of proteins of white adipose tissue (WAT) and brown adipose tissue (BAT) in obesity and explore the underlying mechanisms on energy metabolism. Methods C57BL/6J mice were fed with normal diet (ND, n = 6) or high-fat diet (HFD, n = 12) for 22 weeks. HFD-induced obese mice were treated with metformin (MET, n = 6). After treatment for 8 weeks, oral glucose tolerance test (OGTT) and hyperinsulinemic–euglycemic clamp were performed to evaluate the improvement of glucose tolerance and insulin sensitivity. Protein expressions of WAT and BAT in mice among ND, HFD, and MET group were identified and quantified with isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC–MS/MS. The results were analyzed by MASCOT, Scaffold and IPA. Results The glucose infusion rate in MET group was increased significantly compared with HFD group. We identified 4388 and 3486 proteins in WAT and BAT, respectively. As compared MET to HFD, differential expressed proteins in WAT and BAT were mainly assigned to the pathways of EIF2 signaling and mitochondrial dysfunction, respectively. In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly. Conclusions Metformin improved the body weight and insulin sensitivity of obese mice. Meanwhile, metformin might ameliorate endoplasmic reticulum stress in WAT, and affect fatty acid metabolism in WAT and BAT. CPT1 might be a potential target of metformin in WAT and BAT.


1987 ◽  
Vol 252 (3) ◽  
pp. E391-E395 ◽  
Author(s):  
I. Vatnick ◽  
R. S. Tyzbir ◽  
J. G. Welch ◽  
A. P. Hooper

Rapidly regressing perirenal brown adipose tissue (BAT) of neonatal goats was studied to correlate changes in mitochondrial metabolism and thermogenic capacity with changes in mitochondrial structure. The alpha-glycerophosphate shuttle activity of perirenal BAT mitochondria declined 60% from birth to 6 days of age. Oxygen consumption and thermogenic capacity measured by ion conductance peaked at birth and declined to low levels at 6 days. Sample electron micrographs of perirenal BAT showed intact electron-dense mitochondria with many cristae and little matrix area at 2 days. However, by 6 days the mitochondria were very relaxed with large matrix area, few cristae, and observable degradation. These results indicate that the morphological changes exhibited by rapidly regressing goat's perirenal BAT in the 1st wk postpartum are accompanied by dramatic alterations in BAT mitochondrial function.


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