Cold exposure – an approach to increasing energy expenditure in humans

Lichtenbelt, Wouter van Marken; Kingma, Boris; Lans, Anouk van der; Schellen, L Lisje

doi:10.1016/j.tem.2014.01.001

Cited by 86 publications

(78 citation statements)

References 12 publications

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“…The promotion of BAT activity and, especially, of WAT browning are active research areas that hold promise for strategies aimed at protecting against obesity and associated metabolic abnormalities (e.g. hyperglycaemia and hyperlipidaemia) [24,25]. Here, we report that both cold exposure and chronic treatment with a β 3 -adrenergic agonist (two validated models for inducing WAT browning [20,26]) were associated with dramatic decreases in Lbp gene expression in iWAT.…”

Section: Discussionmentioning

confidence: 87%

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Lipopolysaccharide-binding protein is a negative regulator of adipose tissue browning in mice and humans

et al. 2016

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Aims/hypothesis Adipocyte lipopolysaccharide-binding protein (LBP) biosynthesis is associated with obesity-induced adipose tissue dysfunction. Our purpose was to study the role of LBP in regulating the browning of adipose tissue. Methods Adult mice were maintained at 4°C for 3 weeks or treated with the β 3 -adrenergic agonist, CL316,243, for 1 week to induce the browning of white fat. Precursor cells from brown and white adipose tissues were cultured under differentiation-inducing conditions to yield brown and beige/ brite adipocytes, respectively. In vitro, Lbp was knocked down in 3T3-L1 adipocytes, and cells were treated with recombinant LBP or co-cultured in transwells with control 3T3-L1 adipocytes. Wild-type and Lbp-null mice, fed a standard or high fat diet (HFD) for 15 weeks, were also used in investigations. In humans, subcutaneous and visceral adipose tissue samples were obtained from a cohort of morbidly obese participants.Results The induction of white fat browning by exposure of mice to cold or CL316,243 treatment was strongly associated with decreased Lbp mRNA expression in white adipose tissue. The acquisition of the beige/brite phenotype in cultured cells was associated with downregulation of Lbp. Moreover, silencing of Lbp induced the expression of brown fat-related genes in adipocytes, whereas LBP treatment reversed this effect. Lbp-null mice exhibited the spontaneous induction of subcutaneous adipose tissue browning, as evidenced by a remarkable increase in Ucp1 and Dio2 gene expression and the appearance of multivacuolar adipocyte clusters. The amount of brown adipose tissue, and brown adipose tissue activity were also increased in Lbp-null mice. These changes were associated with decreased weight gain in Lbp-null mice and protection against HFD-induced inflammatory responses, as shown by reduced IL-6 levels. However, rather than improving glucose homeostasis, these effects led to glucose intolerance and insulin resistance. Conclusions/interpretation LBP is identified as a negative regulator of the browning process, which is likely to contribute to the obesity-promoting action of LBP. The deleterious metabolic effects of LBP deletion are compatible with the concept that the appropriate regulation of inflammatory pathways is necessary for a healthy systemic metabolic profile, regardless of body weight regulation.

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Section: Discussionmentioning

confidence: 87%

“…Lbp-null mice exhibit reduced body weight gain accompanied by an induction of the browning process in iWAT To study the role of LBP in vivo, Lbp-null mice and WT littermate controls were fed standard chow (CTRL) or an 25 5,000 4,000 3,000 2,000 8 (n-v) Transcript levels of (n) Lbp,…”

Section: Resultsmentioning

confidence: 99%

Lipopolysaccharide-binding protein is a negative regulator of adipose tissue browning in mice and humans

et al. 2016

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“…It will remain very important that public health initiatives stress the health dangers of physical inactivity and overeating; the coming years will also reveal whether a lack of time outside the thermoneutral zone should be considered an additional danger to health. Based on the results to date, it can be hypothesised that regular exposure to mild cold may become-together with exercise and weight loss-a third lifestyle factor that can be used to stimulate health [17]. As with lifestyle and exercise, we need to understand how much cold is enough; are we facing a '30 min of cold per day keeps the doctor away' advice, or will 30 min of cold per day not be sufficient to counterbalance being in the thermoneutral zone…”

Section: Towards New Therapies For Diabetes and Metabolic Complicatiomentioning

confidence: 99%

The future of brown adipose tissues in the treatment of type 2 diabetes

2015

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The recent recognition that humans possess active depots of brown adipose tissue has boosted the interest in this tissue as a potential target for the prevention and treatment of obesity and related metabolic disorders. Furthermore, it was also revealed that brown adipose tissue (BAT) in humans may consist of so-called beige or brite adipocytes. So far, cold exposure is recognised as the strongest activator of BAT in humans, but there is much ongoing research focused on finding alternative activators of BAT. The consequences of longterm BAT activation and/or cold exposure on metabolic health are still unknown, and this represents an area of intensive research. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965Diabetologia ( -2015.

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“…The recent interest in brown adipose tissue has led to a reappraisal of earlier work [85] on the benefit of reduced ambient temperature in the treatment of obesity [86]. Some fat loss was observed in a 6-week study [87].…”

Section: Cold Capsaicin and Nicotinementioning

confidence: 99%

Horizons in the Pharmacotherapy of Obesity

Arch

2015

Curr Obes Rep

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Abstract:Obesity drugs have had a chequered history. In the recent past, only the low efficacy, pancreatic lipase inhibitor orlistat was available worldwide and it was little used. The 5HT2C agonist lorcaserin, and two combinations of old drugs have been approved in the United States but not in Europe. The diabetes drug liraglutide has been approved in both the US and Europe and seems likely to be most widely accepted. In view of regulators' caution in approving obesity drugs, some (like beloranib) may initially be progressed for niche obesity markets. New drug targets have been identified in brown adipose tissue with the aim of not only activating thermogenesis but also increasing the capacity for thermogenesis in this tissue. Attempts are being made to match the efficacy of bariatric surgery by mimicking multiple gut hormones. Unapproved pharmacotherapies are tempting for some patients. Others remain optimistic about more conventional routes to pharmacotherapy.3

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Cold exposure – an approach to increasing energy expenditure in humans

Cited by 86 publications

References 12 publications

Lipopolysaccharide-binding protein is a negative regulator of adipose tissue browning in mice and humans

Lipopolysaccharide-binding protein is a negative regulator of adipose tissue browning in mice and humans

The future of brown adipose tissues in the treatment of type 2 diabetes

Horizons in the Pharmacotherapy of Obesity

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