Adipocyte size predicts incidence of type 2 diabetes in women

Lönn, Malin; Mehlig, Kirsten; Bengtsson, Calle; Lissner, Lauren

doi:10.1096/fj.09-133058

Cited by 177 publications

(144 citation statements)

References 40 publications

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“…Furthermore, genetic predisposition for type 2 diabetes associates with adipocyte hypertrophy in non-obese first-degree relatives [29]. Finally, several studies show that enlarged fat cell size confers an increased risk of developing type 2 diabetes [10,11,30]. When these findings are put together it is tempting to speculate that scWAT hypertrophy independent of excess body fat is an important defect, which triggers local inflammation and impaired lipolysis and these, in turn, facilitate the development of type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

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Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes

et al. 2015

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Aims/hypothesis We aimed to elucidate the impact of fat cell size and inflammatory status of adipose tissue on the development of type 2 diabetes in non-obese individuals. Methods We characterised subcutaneous abdominal adipose tissue by examining stromal cell populations by 13 colour flow cytometry, measuring expression of adipogenesis genes in the progenitor cell fraction and determining lipolysis and adipose secretion of inflammatory proteins in 14 non-obese men with type 2 diabetes and 13 healthy controls matched for age, sex, body weight and total fat mass. Results Individuals with diabetes had larger fat cells than the healthy controls but stromal cell population frequencies, adipose lipolysis and secretion of inflammatory proteins did not differ between the two groups. However, in the entire cohort fat cell size correlated positively with the ratio of M1/M2 macrophages, TNF-α secretion, lipolysis and insulin resistance. Expression of genes encoding regulators of adipogenesis and adipose morphology (BMP4, CEBPα [also known as CEBPA], PPARγ [also known as PPARG] and EBF1) correlated negatively with fat cell size. Conclusions/interpretation We show that a major phenotype of white adipose tissue in non-obese individuals with type 2 diabetes is adipocyte hypertrophy, which may be mediated by an impaired adipogenic capacity in progenitor cells. Consequently, this could have an impact on adipose tissue inflammation, release of fatty acids, ectopic fat deposition and insulin sensitivity.

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Section: Discussionmentioning

confidence: 99%

“…Thus, increased fat cell size is associated with increased risk of developing type 2 diabetes independently of BMI [10,11]. Moreover, non-obese individuals with heredity for type 2 diabetes display WAT hypertrophy and insulin resistance [12].…”

Section: Introductionmentioning

confidence: 99%

Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes

et al. 2015

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“…10 In this rat model of early type 2 diabetes, we also observed a significant shift toward larger adipocytes in visceral and subcutaneous adipose tissue depots, 12 also reminiscent of the adipocyte phenotype observed in patients with prediabetes. 13,14 In our rat model of early type 2 diabetes, a 6-week treatment with the C21/M24 AT2R agonist restored normal adipocyte size distribution in visceral and subcutaneous adipose tissue depots. 12 Similar conclusions were recently published in a model of high-fat diet and obesity in female mice.…”

Section: Introductionmentioning

confidence: 82%

Postprandial fatty acid uptake and adipocyte remodeling in angiotensin type 2 receptor-deficient mice fed a high-fat/high-fructose diet

et al. 2015

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The role of the angiotensin type-2 receptor in adipose physiology remains controversial. The aim of the present study was to demonstrate whether genetic angiotensin type-2 receptor-deficiency prevents or worsens metabolic and adipose tissue morphometric changes observed following a 6-week high-fat/high-fructose diet with injection of a small dose of streptozotocin. We compared tissue uptake of nonesterified fatty acid and dietary fatty acid in wild-type and angiotensin type-2 receptor-deficient mice by using the radiotracer 14(R,S)-[ 18 F]-fluoro-6-thia-heptadecanoic acid in mice fed a standard or high-fat diet. Postprandial fatty acid uptake in the heart, liver, skeletal muscle, kidney and adipose tissue was increased in wild-type mice after a high-fat diet and in angiotensin type-2 receptor-deficient mice on both standard and high-fat diets. Compared to the wild-type mice, angiotensin type-2 receptor-deficient mice had a lower body weight, an increase in fasting blood glucose and a decrease in plasma insulin and leptin levels. Mice fed a high-fat diet exhibited increased adipocyte size that was prevented by angiotensin type-2 receptor-deficiency. Angiotensin type-2 receptor-deficiency abolished the early hypertrophic adipocyte remodeling induced by a high-fat diet. The small size of adipocytes in the angiotensin type-2 receptor-deficient mice reflects their inability to store lipids and explains the increase in fatty acid uptake in nonadipose tissues. In conclusion, a genetic deletion of the angiotensin type-2 receptor is associated with metabolic dysfunction of white adipose depots, and indicates that adipocyte remodeling occurs before the onset of insulin resistance in the high-fat fed mouse model.

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“…Hypertrophic adipocytes have been associated with hypertension (111) and an increased risk of CVD (112) , and further research in human subjects and mice has found that adipocyte size positively correlates with degree of AT inflammation (113)(114)(115)(116) . Hypertrophic adipocytes isolated from human subjects have been found to have altered gene expression (117) leading to increased secretion of pro-inflammatory factors and altered adipokine secretion (118)(119)(120) .…”

Section: Adipocyte Hypertrophymentioning

confidence: 99%

Pathogenic obesity and nutraceuticals

2011

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Over a decade of intense research in the field of obesity has led to the knowledge that chronic, excessive adipose tissue expansion leads to an increase in the risk for CVD, type 2 diabetes mellitus and cancer. This is primarily thought to stem from the low-grade, systemic inflammatory response syndrome that characterises adipose tissue in obesity, and this itself is thought to arise from the complex interplay of factors including metabolic endotoxaemia, increased plasma NEFA, hypertrophic adipocytes and localised hypoxia. Plasma concentrations of vitamins and antioxidants are lower in obese individuals than in the non-obese, which is hypothesised to negatively affect the development of inflammation and disease in obesity. This paper provides a review of the current literature investigating the potential of nutraceuticals to ameliorate the development of oxidative stress and inflammation in obesity, thereby limiting the onset of obesity complications. Research has found nutraceuticals able to positively modulate the activity of adipocyte cell lines and further positive effects have been found in other aspects of pathogenic obesity. While their ability to affect weight loss is still controversial, it is clear that they have a great potential to reverse the development of overweight and obesity-related comorbidities; this, however, still requires much research especially that utilising well-structured randomised controlled trials.

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Adipocyte size predicts incidence of type 2 diabetes in women

Cited by 177 publications

References 40 publications

Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes

Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes

Postprandial fatty acid uptake and adipocyte remodeling in angiotensin type 2 receptor-deficient mice fed a high-fat/high-fructose diet

Pathogenic obesity and nutraceuticals

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