Faculty Opinions recommendation of Inhibition of Mitochondrial Calcium Overload by SIRT3 Prevents Obesity- or Age-Related Whitening of Brown Adipose Tissue.

2020 ◽  
Author(s):  
Jin-Xiong She ◽  
Cong-Yi Wang
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Calcium Overload ◽  
Mitochondrial Calcium ◽  
Age Related ◽  
Brown Adipose

scholarly journals Inhibition of Mitochondrial Calcium Overload by SIRT3 Prevents Obesity- or Age-Related Whitening of Brown Adipose Tissue

Diabetes ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 165-180 ◽  
Author(s):  
Peng Gao ◽  
Yanli Jiang ◽  
Hao Wu ◽  
Fang Sun ◽  
Yaohong Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Calcium Overload ◽  
Mitochondrial Calcium ◽  
Age Related ◽  
Brown Adipose

Abstract 12631: Peripheral Gamma-aminobutyric Acid(gaba) Signaling in Brown Adipose Tissue Induces Metabolic Dysfunction in Obesity

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ryutaro Ikegami ◽  
Ippei Shimizu ◽  
Takeshi Sato ◽  
Shuang Jiao ◽  
Yohko Yoshida ◽  
...  
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Function ◽  
Aminobutyric Acid ◽  
Mitochondrial Calcium ◽  
Metabolic Dysfunction ◽  
Gamma Aminobutyric Acid ◽  
Brown Adipose ◽  
Gaba Signaling

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.

Differential Responses of White Adipose Tissue and Brown Adipose Tissue to Calorie Restriction During Aging

2020 ◽  
Author(s):  
Yunlu Sheng ◽  
Fan Xia ◽  
Lei Chen ◽  
Yifan Lv ◽  
Shan Lv ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Metabolic Disorder ◽  
Energy Homeostasis ◽  
Nutritional Intervention ◽  
Metabolic Health ◽  
Protective Effects ◽  
Age Related ◽  
Brown Adipose

Abstract Age-related adipose tissue dysfunction is potentially important in the development of insulin resistance and metabolic disorder. Caloric restriction (CR) is a robust intervention to reduce adiposity, improve metabolic health, and extend healthy life span. Both white adipose tissue (WAT) and brown adipose tissue (BAT) are involved in energy homeostasis. CR triggers the beiging of WAT in young mice; however, the effects of CR on beiging of WAT and function of BAT during aging are unclear. This study aimed to investigate how age and CR impact the beiging of WAT, the function of BAT, and metabolic health in mice. C57BL/6 mice were fed CR diet (40% less than the ad libitum [AL] diet) for 3 months initiated in young (3 months), middle-aged (12 months), and old (19 months) stage. We found age-related changes in different types of adipose tissue, including adipocyte enlargement, declined beiging of WAT, and declined thermogenic and β-oxidational function of BAT. Moreover, CR attenuated age-associated adipocyte enlargement and prevented the age-related decline in beiging potential of WAT. These protective effects on the beiging potential were significant in inguinal WAT at all three ages, which were significant in epididymal WAT at young and old age. In contrast, thermogenic and β-oxidational function of BAT further declined after CR in the young age group. In conclusion, our findings reveal the contribution of WAT beiging decline to age-related metabolic disorder and suggest nutritional intervention, specifically targeting WAT beiging, as an effective approach to metabolic health during aging.

scholarly journals Orexin Restores Aging-Related Brown Adipose Tissue Dysfunction in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 485-501 ◽  
Author(s):  
Dyan Sellayah ◽  
Devanjan Sikder
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Fat Mass ◽  
Core Body Temperature ◽  
Brown Adipocyte ◽  
Aged Mice ◽  
Age Related ◽  
Brown Adipose ◽  
The Impact

The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. In vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphologic characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy. Our results suggest a role for orexin (OX) signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.

Age-Related Decrease in Cold-Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans

Obesity ◽  
2011 ◽  
Vol 19 (9) ◽  
pp. 1755-1760 ◽  
Author(s):  
Takeshi Yoneshiro ◽  
Sayuri Aita ◽  
Mami Matsushita ◽  
Yuko Okamatsu-Ogura ◽  
Toshimitsu Kameya ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Body Fat ◽  
Healthy Humans ◽  
Age Related ◽  
Brown Adipose

scholarly journals Deletion of Letmd1 leads to the disruption of mitochondrial function in brown adipose tissue

2020 ◽  
Author(s):  
Runjie Song ◽  
Yaqi Du ◽  
Peng Li ◽  
Huijiao Liu ◽  
Han Zheng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Mitochondrial Calcium ◽  
List Type ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Clinical Biomarker ◽  
Mitochondrial Membrane Protein

AbstractHuman cervical cancer oncogene (HCCR-1), also named as LETMD1, is a LETM-domain containing outer mitochondrial membrane protein which plays an important role in the carcinogenesis of cancers. Surprisingly, we found that loss of Letmd1 in mice leads to multiply severe abnormities, such as the brown adipose tissue (BAT) whitening, disruption of thermogenesis, cold-induced death, diet-induced obesity, hyperglycinemia and insulin resistance. Mechanistically, deletion of Letmd1 in BAT causes the reduction of mitochondrial calcium ion, which in turn results in the suppressed fission of mitochondria, and ultimately leads to the depletion of Ucp1-mediated BAT heat production. This study indicates that LETMD1 plays a crucial role in controlling BAT thermogenesis and energy homeostasis by regulating mitochondrial structures and functions, and also provides a novel insight for the clinical biomarker and therapeutical target of oncogene for the metabolic disorders.HighlightsLetmd1 is an oncogene and also highly expressed in brown adipose tissue (BAT) of human and mice.Loss of Letmd1 leads to BAT whitening, diet-induced obesity, hyperglycemia and insulin resistant.Letmd1 knockout causes the disruption of thermogenesis and death at 4°C exposure.Deletion of Letmd1 results in mitochondrial calcium homeostasis disorders.Graphic abstract

Impact of UCP1 and β3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans

2012 ◽  
Vol 37 (7) ◽  
pp. 993-998 ◽  
Author(s):  
T Yoneshiro ◽  
T Ogawa ◽  
N Okamoto ◽  
M Matsushita ◽  
S Aita ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Gene Polymorphisms ◽  
Age Related ◽  
Brown Adipose ◽  
Age Related Changes

scholarly journals Loss of FSTL1-expressing adipocyte progenitors drives the age-related involution of brown adipose tissue

2020 ◽  
Author(s):  
Zan Huang ◽  
Zengdi Zhang ◽  
Ryan Heck ◽  
Ping Hu ◽  
Hezkiel Nanda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Brown Adipocyte ◽  
List Type ◽  
Cellular Mechanisms ◽  
Age Related ◽  
Brown Adipose ◽  
Adipocyte Progenitors ◽  
Genetic Deletion

SUMMARYIn humans, brown adipose tissue (BAT) undergoes progressive involution or atrophy with increasing age, as manifested by decreased prevalence and mass, transformation to white adipose tissue (WAT), and reduction in thermogenic activity. This involution process cannot be fully recapitulated in rodent models and thus underlying cellular mechanisms are poorly understood. Here, we show that the interscapular BAT (iBAT) in rabbits involutes rapidly in early life, similarly to that in humans. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied with the loss of brown adipogenic competence of their precursor cells. Through single-cell RNA sequencing, we surveyed the heterogenous populations of mesenchymal cells within the stromal vascular fraction of rabbit and human iBAT. An analogous FSTL1high population of brown adipocyte progenitors exists in both species while gradually disappear during iBAT involution in rabbits. In mice, FSTL1 is highly expressed by adipocyte progenitors in iBAT and genetic deletion of FSTL1 causes defective WNT signaling and iBAT atrophy in neonates. Our results underscore the BAT-intrinsic contribution from FSTL1high progenitors to age-related tissue involution and point to a potential therapeutic approach for obesity and its comorbidities.HIGHLIGHTSRabbit BAT irreversibly transforms to WAT before puberty.iBAT adipocyte progenitors reprogram transcriptome and lose brown adipogenic ability.Comparable FSTL1high brown adipocyte progenitors exist in rabbit and human iBAT.Loss of FSTL1 in brown adipocyte progenitors causes iBAT atrophy in mice.

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