Metabolic responses to mild cold acclimation in type 2 diabetes patients

Remie, Carlijn M. E.; Moonen, Michiel P.B.; Roumans, Kay H. M.; Nascimento, Emmani B. M.; Gemmink, Anne; Havekes, Bas; Schaart, Gert; Kornips, Esther; Joris, Peter J.; Schrauwen‐Hinderling, Vera B.; Hoeks, Joris; Kersten, Sander; Hesselink, Matthijs K. C.; Phielix, Esther; Lichtenbelt, Wouter D. van Marken; Schrauwen, Patrick

doi:10.1038/s41467-021-21813-0

Cited by 15 publications

(11 citation statements)

References 36 publications

(40 reference statements)

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“…For example, a study quantifying BAT activation and whole-body glucose metabolism in patients with T2DM after 10 days of cold acclimation showed only a small increase in [ 18 F]FDG uptake by BAT despite a marked improvement in glucose metabolism [ 128 ]. In a follow-up study, the experiment was repeated, but shivering was prevented, leading to a complete reduction of the favorable effects [ 129 ]. This suggests that either muscle contraction (shivering) or a strong cold stimulus is needed to stimulate the positive effects of BAT.…”

Section: Discussionmentioning

confidence: 99%

The Role of AMPK Signaling in Brown Adipose Tissue Activation

Vaart

Boon

Houtkooper

2021

Cells

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Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

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Section: Discussionmentioning

confidence: 99%

The Role of AMPK Signaling in Brown Adipose Tissue Activation

Vaart

Boon

Houtkooper

2021

Cells

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“…However, cold exposure increases shivering and glucose uptake of several large groups of postural skeletal muscles that account for approximately 50% of systemic glucose production vs approximately 1% for BAT during cold exposure ( 405 ). A more recent study confirmed the importance of the muscle shivering response in cold-acclimation–induced whole-body IS in participants with T2D ( 666 ).…”

Section: Brown Adipose Tissue In Cardiometabolic Diseasesmentioning

confidence: 72%

Brown Adipose Tissue—A Translational Perspective

et al. 2022

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Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography (PET) with 18F-fluorodeoxiglucose ( 18FDG), which can be dissociated from BAT thermogenic activity, as for example in insulin resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride (TG) lipolysis. This lipolytic BAT response is intertwined with that of white adipose and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body’s thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in white adipose and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.

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“…Hyperlipidemic patients with obesity and type 2 diabetes characterized by high plasma TG and low plasma HDL-cholesterol concentrations have been reported to exhibit lower thermogenic adipocyte activity than that in healthy subjects [ 4 , 168 ]. In addition, it has been demonstrated that the expression of UCP1 in human epicardial fat is positively correlated with lower plasma TG and higher plasma HDL-cholesterol levels [ 169 ].…”

Section: Bat Dysfunction In Metabolic Diseasesmentioning

confidence: 99%

The Role and Regulatory Mechanism of Brown Adipose Tissue Activation in Diet-Induced Thermogenesis in Health and Diseases

Chan

Hsieh

2022

IJMS

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Brown adipose tissue (BAT) has been considered a vital organ in response to non-shivering adaptive thermogenesis, which could be activated during cold exposure through the sympathetic nervous system (SNS) or under postprandial conditions contributing to diet-induced thermogenesis (DIT). Humans prefer to live within their thermal comfort or neutral zone with minimal energy expenditure created by wearing clothing, making shelters, or using an air conditioner to regulate their ambient temperature; thereby, DIT would become an important mechanism to counter-regulate energy intake and lipid accumulation. In addition, there has been a long interest in the intriguing possibility that a defect in DIT predisposes one to obesity and other metabolic diseases. Due to the recent advances in methodology to evaluate the functional activity of BAT and DIT, this updated review will focus on the role and regulatory mechanism of BAT biology in DIT in health and diseases and whether these mechanisms are applicable to humans.

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Metabolic responses to mild cold acclimation in type 2 diabetes patients

Cited by 15 publications

References 36 publications

The Role of AMPK Signaling in Brown Adipose Tissue Activation

The Role of AMPK Signaling in Brown Adipose Tissue Activation

Brown Adipose Tissue—A Translational Perspective

The Role and Regulatory Mechanism of Brown Adipose Tissue Activation in Diet-Induced Thermogenesis in Health and Diseases

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