Brown adipocyte glucose metabolism: a heated subject

Hankir, Mohammed K.; Klingenspor, Martin

doi:10.15252/embr.201846404

Cited by 100 publications

(84 citation statements)

References 117 publications

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“…Non-shivering thermogenesis is fuelled by different sources, including glucose, succinate (Mills et al, 2018), branched-chain amino acids (Yoneshiro et al, 2019), and fatty acids (FAs) (Cannon and Nedergaard, 2004;Townsend and Tseng, 2014). In rodents, glucose is a major fuel, with ~20% of circulating glucose being consumed by BAT under basal conditions (Hankir and Klingenspor, 2018). FAs, derived from triglycerides (TGs) stored in lipid droplets (LDs) of brown adipocytes, from white adipose tissue (WAT) lipolysis (Schreiber et al, 2017), or from TG-rich lipoproteins in the circulation (Bartelt et al, 2011), are other major fuels.…”

Section: Introductionmentioning

confidence: 99%

Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis

Chitraju

Fischer

Farese

et al. 2020

Preprint

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Brown adipocytes store metabolic energy as triglycerides (TG) in multilocular lipid droplets (LDs). Fatty acids released from brown adipocyte LDs by lipolysis are thought to activate and fuel UCP1-mediated thermogenesis. Here we test this hypothesis by preventing fatty acid storage in murine brown adipocytes through brown adipose tissue (BAT)-specific deletions of the TG synthesis enzymes, DGAT1 and DGAT2 (BA-DGAT KO). Despite the absence of LDs, BA-DGAT KO mice had functional BAT and maintained euthermia during acute or chronic cold exposure. As apparent adaptations to the lack of TG, brown adipocytes of BA-DGAT KO mice appear to utilize circulating glucose and fatty acids, as well as stored glycogen to fuel thermogenesis. Moreover, BA-DGAT KO mice were resistant to diet-induced glucose intolerance, likely due to increased glucose disposal by BAT. Thus, surprisingly, TGs in BAT are dispensable for its function, in part through adaptations to utilize other fuel sources.

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Section: Introductionmentioning

confidence: 99%

Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis

Chitraju

Fischer

Farese

et al. 2020

Preprint

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“…During thermogenesis, adipose depots exploit amino acid, glucose and fatty acid degradation to sustain the uncoupling activity of Ucp1 (Hankir and Klingenspor, 2018;Rose and Richter, 2009;Yoneshiro et al, 2019). Based on our results it can be postulated that changes in the macronutrient ratio, i.e.…”

Section: Discussionmentioning

confidence: 59%

Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue

Aquilano

Sciarretta

Turchi

et al. 2020

Preprint

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Low-protein/high-carbohydrate (LPHC) diet promotes metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1-and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.

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“…Brown adipose tissue (BAT), with its unique ability to dissipate excessive energy in form of heat through mitochondrial uncoupling, plays an important role in regulating body temperature, but also glucose and lipid homeostasis and consequently body weight (Klepac, Georgiadi et al, 2019, Nedergaard & Cannon, 2018, Townsend & Tseng, 2014. Importantly, BAT activity itself is tightly regulated by environmental signals, as well as the metabolic state of the organism (Hankir & Klingenspor, 2018, Heeren & Scheja, 2018, Hoeke, Kooijman et al, 2016, Li, Schnabl et al, 2018, Mills, Pierce et al, 2018, Oelkrug, Polymeropoulos et al, 2015, Okla, Kim et al, 2017, Ramirez, Lynes et al, 2017. This underscores the important role of BAT as rheostat sensing the organismal state to regulate whole body metabolic function through a complex network of neuronal, endocrine and nutritional inputs.…”

Section: Introductionmentioning

confidence: 99%

“…The role of the sympathetic nervous system, as well as glucose, fatty acids and other metabolites have been extensively described in the regulation of BAT activity (Hankir, Cowley et al, 2016, Hankir & Klingenspor, 2018, Heeren & Scheja, 2018, Hoeke et al, 2016, Kuruvilla, 2019. However, surprisingly little is known about the potential role of amino acids in the regulation of BAT function.…”

Section: Introductionmentioning

confidence: 99%

PAT2 regulates autophagy through vATPase assembly and lysosomal acidification in brown adipocytes

Wang

Krueger

Hauck

et al. 2020

Preprint

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2 Brown adipose tissue (BAT) plays a key role in maintaining body temperature as well as glucose and lipid homeostasis by its ability to dissipate energy through mitochondrial uncoupling. To facilitate these tasks BAT needs to adopt its thermogenic activity and substrate utilization to changes in nutrient availability, regulated by a complex network of neuronal, endocrine and nutritional inputs. Amongst this multitude of factors influencing BAT activity changes in the autophagic response of brown adipocytes are an important regulator of its thermogenic capacity and activity. Increasing evidence supports an important role of amino acid transporters in mTORC1 activation and the regulation of autophagy. However, a specific role of amino acid transporters in BAT regulating its function has not been described. Here we show that the brown adipocyte specific proton coupled amino acid transporter PAT2 rapidly translocates from the plasma membrane to the lysosome in response to amino acid withdrawal, where it facilitates the assembly of the lysosomal vATPase. Loss or overexpression of PAT2 therefore impair lysosomal acidification, autophagolysosome formation and starvation induced mTORC1 activation.

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Brown adipocyte glucose metabolism: a heated subject

Cited by 100 publications

References 117 publications

Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis

Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis

Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue

PAT2 regulates autophagy through vATPase assembly and lysosomal acidification in brown adipocytes

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