Lipolysis in Brown Adipocytes Is Not Essential for Cold-Induced Thermogenesis in Mice

Shin, Hyunsu; Ma, Yinyan; Chanturiya, Tatyana; Cao, Qiang; Wang, Youlin; Kadegowda, Anil K. G.; Jackson, Rachel; Rumore, Dominic; Xue, Bingzhong; Shi, Hang; Гаврилова, Оксана; Yu, Liqing

doi:10.1016/j.cmet.2017.09.002

Cited by 218 publications

(226 citation statements)

References 65 publications

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“…Conversely, there is also evidence that lipolysis is not energetically critical for heat production in BAT. Others have observed that in the absence of BAT lipolysis during cold acclimation, thermoregulation is supported by iWAT lipolysis under fasting conditions or by diet nutrients [34]. However, in our study, long-term cold challenge had no effect on iWAT weight.…”

Section: Demonstrated Thatcontrasting

confidence: 88%

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Trpm8 modulates thermogenesis in a sex-dependent manner without influencing cold-induced bone loss

Carvalho

Treyball

Brooks

et al. 2020

Preprint

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Trpm8 (transient receptor potential cation channel, subfamily M, member 8) is expressed by sensory neurons, and it is involved in the detection of cold temperatures. Increased Trpm8 expression triggers an increase in uncoupling protein 1 (Ucp1)-dependent brown adipose tissue (BAT) thermogenesis. Here, we sought to investigate whether Trpm8 was involved in the coregulation of thermogenesis and bone homeostasis. We exposed male and female mice with and without Trpm8 to a 3-week cold challenge (4°C). Male Trpm8-KO mice exhibited a delayed cold acclimation with increased BAT expression of Ucp1, Dio2 and Cidea. Conversely, female mice had no genotype-specific alterations in body temperature. Interestingly, Trpm8 was not required for cold-induced bone loss. In summary, we identified an intriguing sex difference in the role of Trpm8 in maintaining body temperature and composition. Furthermore, although global Trpm8 deletion did not affect bone response to cold, it did influence cortical bone shape.Summary pop-up windows provided the individual and average area (mm 2 ) for each counted adipocyte within the T.Ar; these data were used to quantify adiposity in each sample (based on adipocyte number and average adipocyte area). Micro-computed tomography (µCT)A high-resolution desktop micro-tomographic imaging system (μCT40, Scanco Medical AG, Brüttisellen, Switzerland) was used to assess trabecular bone architecture in the distal femoral metaphysis and L5 vertebral body and cortical bone morphology of the femoral middiaphysis. Scans were acquired using a 10 μm 3 isotropic voxel size, 70 kVP, 114 μA, 200 ms integration time, and were subjected to Gaussian filtration and segmentation. Image acquisition Reverse: 5'-CTT TGC CTC ACT CAG GAT TGG -3' Cooper et al. (2008)

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Section: Demonstrated Thatcontrasting

confidence: 88%

“…Cooling sensitivity is the first step to activate the cold response neuronal mechanism that modulates lipolysis and energy expenditure [34]. Cold-induced metabolic changes are more pronounced in BAT compared to WAT depots [35].…”

Section: Demonstrated Thatmentioning

confidence: 99%

Trpm8 modulates thermogenesis in a sex-dependent manner without influencing cold-induced bone loss

Carvalho

Treyball

Brooks

et al. 2020

Preprint

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“…Thereto, mice treated with a A 2A agonist exhibit increased energy expenditure as well as resilience to the effects of high-fat diet feeding as illustrated by improved glucose tolerance and a leaner phenotype than control mice [51]. In brown and beige adipocytes, lipolysis is central, but not indispensable, for thermogenesis and Ucp1dependent uncoupling [52][53][54][55].…”

Section: Browning/beiging Signalsmentioning

confidence: 99%

The weight of nutrients: kynurenine metabolites in obesity and exercise

et al. 2018

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Obesity ultimately results from an imbalance between energy intake and expenditure. However, in addition to their bioenergetic value, nutrients and their metabolites can function as important signalling molecules in energy homeostasis. Indeed, macronutrients and their metabolites can be direct regulators of metabolism through their actions on different organs. In turn, target organs can decide to use, store or transform the incoming nutrients depending on their physiological context and in coordination with other cell types. Tryptophan-kynurenine metabolites are an example of a family of compounds that can serve as systemic integrators of energy metabolism by signalling to different cell types. These include adipocytes, immune cells and muscle fibres, in addition to the well-known effects of kynurenine metabolites on the central nervous system. In the context of energy metabolism, several of the effects elicited by kynurenic acid are mediated by the G-protein-coupled receptor, GPR35. As GPR35 is expressed in tissues such as the adipose tissue, immune cells and the gastrointestinal tract, this receptor could be a potential therapeutic target for the treatment of obesity, diabetes and other metabolic diseases. In addition, metabolic disorders often coincide with states of chronic inflammation, which further highlights GPR35 as an integration node in conditions where inflammation skews metabolism. Defining the molecular interplay between different tissues in the regulation of energy homeostasis can help us understand interindividual variability in the response to nutrient intake and develop safe and efficient therapies to fight obesity and metabolic disease.

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“…The process of lipolysis that generates FFA is thus crucial for normal thermogenesis (Himms-Hagen, 1972). Furthermore, it has been shown that lipolysis in white adipocytes is required to fuel NST (Schreiber et al, 2017;Shin et al, 2017). Several features of the Opn3 germ-line and "minus blue" mice suggested there might be a defect in thermogenesis: In inWAT, Ucp1 transcripts and protein are at low levels, there is low "brite" adipocyte and NAD content and similarly, in iBAT, UCP1 and some ETC complex proteins are at low levels.…”

Section: Adaptive Thermogenesis In Mice Is Promoted By Blue Light Inmentioning

confidence: 99%

“…The long-standing belief that BAT lipolysis is essential for non-shivering thermogenesis has been challenged by recent analysis (Schreiber et al, 2017;Shin et al, 2017). These investigators showed that inhibiting lipolysis in BAT does not impair body temperature maintenance as long as thermogenic fuel was available through WAT lipolysis or dietary sources.…”

Section: White Adipocyte Opn3 Is Required For Normal Lipolysis Duringmentioning

confidence: 99%

Adaptive thermogenesis in mice requires adipocyte light-sensing via Opsin 3

Nayak

Vemaraju

Zhang

et al. 2019

Preprint

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Almost all life forms can decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are interpreted as images, and the circadian system, where light entrains a physiological clock. Here we describe a local, nonvisual light response in mice that employs encephalopsin (OPN3, a 480 nm, blue light responsive opsin) to regulate the function of adipocytes. Germ line null and adipocytespecific conditional null mice show a deficit in thermogenesis that is phenocopied in mice under blue-light deficient conditions. We show that blue light stimulation of adipocytes activates hormone sensitive lipase, the rate limiting enzyme in the lipolysis pathway, and that this is OPN3-dependent. Opn3 adipocyte conditional null mice also use reduced levels of fat mass when fasted and cold exposed further suggesting a lipolysis deficit. These data suggest the hypothesis that in mice, a local, OPN3-dependent light response in adipocytes is a mechanism for regulation of energy homeostasis.

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Lipolysis in Brown Adipocytes Is Not Essential for Cold-Induced Thermogenesis in Mice

Cited by 218 publications

References 65 publications

Trpm8 modulates thermogenesis in a sex-dependent manner without influencing cold-induced bone loss

Trpm8 modulates thermogenesis in a sex-dependent manner without influencing cold-induced bone loss

The weight of nutrients: kynurenine metabolites in obesity and exercise

Adaptive thermogenesis in mice requires adipocyte light-sensing via Opsin 3

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