Age‐Related Decrease in Cold‐Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans

Yoneshiro, Takeshi; Aita, Sayuri; Matsushita, M.; Okamatsu‐Ogura, Yuko; Kameya, Toshimitsu; Kawai, Yuko; Miyagawa, Masao; Tsujisaki, Masayuki; Saito, Masayuki

doi:10.1038/oby.2011.125

Cited by 414 publications

(371 citation statements)

References 24 publications

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“…Some of these studies indicated that not obesity per se, but also insulin resistance contributes significantly to cold intolerance and reduced BAT activity [8,10,11]. In humans, several studies have recently shown negative correlations between BAT activity and adiposity [3,12,13] and age [14]. A negative association between BAT activity and diabetic status, independent of BMI and age, has also been reported in a retrospective study [15].…”

Section: Introductionmentioning

confidence: 73%

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

et al. 2014

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Aims/hypothesis Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation-at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. Methods We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) imaging.Results We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Conclusions/interpretation Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. Trial registration: www.trialregister.nl NTR3523 Funding: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373

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Section: Introductionmentioning

confidence: 73%

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

et al. 2014

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“…A significant decrease in thermogenesis in BAT and browning of WAT has been described as a result of increased age in humans and rodents (Florez‐Duquet, Horwitz, & McDonald, 1998; Pfannenberg et al, 2010; Yoneshiro et al, 2011). We therefore examined the effects of cold exposure in Postn ‐knockout mice and observed a rapid loss of body weight within 72 hr of cold exposure which prevented further long‐term treatments (Figure 3a,b).…”

Section: Resultsmentioning

confidence: 99%

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

et al. 2018

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Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well‐known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue‐resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix‐modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue‐resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high‐fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age‐related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age‐related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.

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“…Additionally, age-dependent loss of thermogenic capacity is associated with a decline in UCP1 activity but not in UCP1 protein (Valle et al 2008). A study on the effect of age on BAT found active BAT in only 10 % of the subjects between 50 and 60 years of age (McDonald and Horwitz 1999;Yoneshiro et al 2011). There are increasing numbers of papers with data interpreted as showing that decreased amounts of brown fat may contribute to thermal dysregulation and energy imbalance often observed in older individuals; however, it is still uncertain whether the methodology for quantifying the number of brown adipocytes and their thermogenic activity in individuals with variable levels of obesity is accurate (Muzik et al 2013).…”

Section: Brown Adipose Tissuementioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

306

203

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Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

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Age‐Related Decrease in Cold‐Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans

Cited by 414 publications

References 24 publications

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

Obesity and related consequences to ageing

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