Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress

Sidossis, Labros S.; Porter, Craig; Saraf, Manish Kumar; Børsheim, Elisabet; Radhakrishnan, Ravi S.; Chao, Tony; Ali, Arham; Chondronikola, Maria; Mlcak, Ronald P.; Finnerty, Celeste C.; Hawkins, Hal K.; Toliver‐Kinsky, Tracy; Herndon, David N.

doi:10.1016/j.cmet.2015.06.022

Cited by 338 publications

(320 citation statements)

References 31 publications

(46 reference statements)

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“…In line with our results, the promotion of BAT activity or the browning of WAT has been reported to result in increased energy expenditure and protection against obesity and type 2 diabetes (35,36,52,53). These preclinical observations together with the recent discovery that browning of scWAT occurs in adult humans make this cell type an attractive therapeutic target for the treatment of obesity and type 2 diabetes (35,53,54). Our results suggest that molecules arising from the ALOX5/ALOX5AP pathway may have potential therapeutic effects.…”

Section: Discussionsupporting

confidence: 90%

ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance

et al. 2016

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Eicosanoids, such as leukotriene B4 (LTB4) and lipoxin A4 (LXA4), may play a key role during obesity. While LTB4 is involved in adipose tissue inflammation and insulin resistance, LXA4 may exert anti-inflammatory effects and alleviate hepatic steatosis. Both lipid mediators derive from the same pathway, in which arachidonate 5-lipoxygenase (ALOX5) and its partner, arachidonate 5-lipoxygenase–activating protein (ALOX5AP), are involved. ALOX5 and ALOX5AP expression is increased in humans and rodents with obesity and insulin resistance. We found that transgenic mice overexpressing ALOX5AP in adipose tissue had higher LXA4 rather than higher LTB4 levels, were leaner, and showed increased energy expenditure, partly due to browning of white adipose tissue (WAT). Upregulation of hepatic LXR and Cyp7a1 led to higher bile acid synthesis, which may have contributed to increased thermogenesis. In addition, transgenic mice were protected against diet-induced obesity, insulin resistance, and inflammation. Finally, treatment of C57BL/6J mice with LXA4, which showed browning of WAT, strongly suggests that LXA4 is responsible for the transgenic mice phenotype. Thus, our data support that LXA4 may hold great potential for the future development of therapeutic strategies for obesity and related diseases.

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Section: Discussionsupporting

confidence: 90%

ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance

et al. 2016

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“…Contrary to mice, in humans gene expression related to browning is more prevalent in visceral than in subcutaneous WAT [95], but whether chronic exposure to low temperature promotes browning of visceral tissue is still not known. These results were confirmed by Sidossis et al [84] who showed that in patients exposed to a prolonged adrenergic stress, such as burn trauma, subcutaneous WAT contains multilocular UCP1-positive adipocytes with increased mitochondrial density and respiratory capacity.…”

Section: Browning Of Wat As a Possible Aid To Fight Metabolic Diseasessupporting

confidence: 66%

“…Although the BAT contribution to human energy expenditure (TEE) is minor, browning has been proposed as a new possible target to fight obesity and improve whole body metabolism and TEE [5], [19], [84].…”

Section: Browning Of Wat As a Possible Aid To Fight Metabolic Diseasesmentioning

confidence: 99%

The color of fat and its central role in the development and progression of metabolic diseases

Gaggini

Carli

Gastaldelli

2017

Hormone Molecular Biology and Clinical Investigation

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Abstract:Excess caloric intake does not always translate to an expansion of the subcutaneous adipose tissue (SAT) and increase in fat mass. It is now recognized that adipocyte type (white, WAT, or brown, BAT), size (large vs. small) and metabolism are important factors for the development of cardiometabolic diseases. When the subcutaneous adipose tissue is not able to expand in response to increased energy intake the excess substrate is stored as visceral adipose tissue or as ectopic fat in tissues as muscle, liver and pancreas. Moreover, adipocytes become dysfunctional (adiposopathy, or sick fat), adipokines secretion is increased, fat accumulates in ectopic sites like muscle and liver and alters insulin signaling, increasing the demand for insulin secretion. Thus, there are some subjects that despite having normal weight have the metabolic characteristics of the obese (NWMO), while some obese expand their SAT and remain metabolically healthy (MHO). In this paper we have reviewed the recent findings that relate the metabolism of adipose tissue and its composition to metabolic diseases. In particular, we have discussed the possible role of dysfunctional adipocytes and adipose tissue resistance to the antilipolytic effect of insulin on the development of impaired glucose metabolism. Finally we have reviewed the possible role of BAT vs. WAT in the alteration of lipid and glucose metabolism and the recent studies that have tried to stimulate browning in human adipose tissue.

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“…In animals, prolonged cold stimulation also induces browning of distinct white adipose tissue (WAT) depots, likely contributing to improved substrate metabolism (7). This phenomenon also has recently been observed in human subcutaneous WAT upon severe and prolonged adrenergic stress (8).…”

Section: Short-term Cold Acclimation Recruits Brown Adipose Tissue Inmentioning

confidence: 82%

“…It is likely that a greater or more prolonged adrenergic stimulus is required to induce browning within these white adipose depots. Sidossis et al (8) recently showed that upon severe and prolonged adrenergic stress (i.e., in burn victims), browning of subcutaneous WAT became apparent, which was associated with increased wholebody EE.…”

Section: Discussionmentioning

confidence: 99%

Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans

et al. 2015

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Recruitment of brown adipose tissue (BAT) has emerged as a potential tool to combat obesity and associated metabolic complications. Short-term cold acclimation has been shown not only to enhance the presence and activity of BAT in lean humans but also to improve the metabolic profile of skeletal muscle to benefit glucose uptake in patients with type 2 diabetes. Here we examined whether short-term cold acclimation also induced such adaptations in 10 metabolically healthy obese male subjects. A 10-day cold acclimation period resulted in increased cold-induced glucose uptake in BAT, as assessed by [18F]fluorodeoxyglucose positron emission tomography/computed tomography. BAT activity was negatively related to age, with a similar trend for body fat percentage. In addition, cold-induced glucose uptake in BAT was positively related to glucose uptake in visceral white adipose tissue, although glucose uptake in visceral and subcutaneous white adipose tissue depots was unchanged upon cold acclimation. Cold-induced skeletal muscle glucose uptake tended to increase upon cold acclimation, which was paralleled by increased basal GLUT4 localization in the sarcolemma, as assessed through muscle biopsies. Proximal skin temperature was increased and subjective responses to cold were slightly improved at the end of the acclimation period. These metabolic adaptations to prolonged exposure to mild cold may lead to improved glucose metabolism or prevent the development of obesity-associated insulin resistance and hyperglycemia.

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Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress

Cited by 338 publications

References 31 publications

ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance

ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance

The color of fat and its central role in the development and progression of metabolic diseases

Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans

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