Weight Gain and Impaired Glucose Metabolism in Women Are Predicted by Inefficient Subcutaneous Fat Cell Lipolysis

Arner, Peter; Andersson, Daniel P.; Bäckdahl, Jesper; Dahlman, Ingrid; Rydén, Mikael

doi:10.1016/j.cmet.2018.05.004

Cited by 102 publications

(96 citation statements)

References 58 publications

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“…Concordant with our current findings, lower nocturnal concentrations of plasma NEFAs during HFOF predict weight gain in obesity-prone individuals (33). Altogether, these results strongly point to a key role for lipolysis in obesity and body weight regulation (38,39).…”

Section: Discussionsupporting

confidence: 91%

Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults

et al. 2019

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The ability to switch fuels for oxidation in response to changes in macronutrient composition of diet (metabolic flexibility) may be informative of individuals’ susceptibility to weight gain. Seventy-nine healthy, weight-stable participants underwent 24-h assessments of energy expenditure and respiratory quotient (RQ) in a whole-room calorimeter during energy balance (EBL) (50% carbohydrate, 30% fat) and then during 24-h fasting and three 200% overfeeding diets in a crossover design. Metabolic flexibility was defined as the change in 24-h RQ from EBL during fasting and standard overfeeding (STOF) (50% carbohydrate, 30% fat), high-fat overfeeding (HFOF) (60% fat, 20% carbohydrate), and high-carbohydrate overfeeding (HCOF) (75% carbohydrate, 5% fat) diets. Free-living weight change was assessed after 6 and 12 months. Compared with EBL, RQ decreased on average by 9% during fasting and by 4% during HFOF but increased by 4% during STOF and by 8% during HCOF. A smaller decrease in RQ, reflecting a smaller increase in lipid oxidation rate, during HFOF but not during the other diets predicted greater weight gain at both 6 and 12 months. An impaired metabolic flexibility to acute HFOF can identify individuals prone to weight gain, indicating that an individual’s capacity to oxidize dietary fat is a metabolic determinant of weight change.

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Section: Discussionsupporting

confidence: 91%

Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults

et al. 2019

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“…This may depend on primary defects in gene expression of specific lipolytic regulators. 7 Aldosterone (ALDO) is a steroid hormone produced by the zona glomerulosa of the adrenal cortex and exerts its effects via mineralocorticoid receptor (MR). While classical effects of ALDO are mediated by MR expressed in renal epithelial cells, 8 MR has also been shown to play a key role in non-epithelial cells including adipocytes.…”

Section: Introductionmentioning

confidence: 99%

The novel non‐steroidal MR antagonist finerenone improves metabolic parameters in high‐fat diet‐fed mice and activates brown adipose tissue via AMPK‐ATGL pathway

et al. 2020

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Mineralocorticoid receptor antagonists (MRAs) are recommended for the treatment of heart failure and hypertension, mainly due to their natriuretic and anti‐fibrotic mode of action. Rodent studies have shown that MRAs can prevent adverse metabolic consequences of obesity but an elucidation of underlying molecular mechanisms is missing. Here, we investigated metabolic effects of the novel non‐steroidal MRA finerenone (FIN) in a mouse model of high‐fat diet (HFD)‐induced obesity and the signaling pathways activated by MR antagonism at level of interscapular brown adipose tissue (iBAT). C57BL/6J male mice were fed a normal diet or a HFD (with60% kcal from fat) containing or not FIN for 3 months. Metabolic parameters, adipose tissue morphology, gene and protein expression analysis were assessed. We also used brown adipocyte cultures (T37i cells) to investigate the effects of FIN‐mediated MR antagonism upon lipid and mitochondrial metabolism. HFD + FIN‐treated mice showed improved glucose tolerance together with increased multilocularity and higher expression of thermogenic markers at the level of iBAT, without differences in white adipose depots, suggesting an iBAT‐specific effect of FIN. Mechanistically, FIN increased activation of AMP‐activated protein kinase which, in turn, stimulated adipose triglyceride lipase activation, with subsequent increased expression of uncoupling protein‐1 in brown adipocytes.

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“…Hence, it remains to be seen how extended periods of weight gain and frequent weight cycling in adulthood affect changes in total adipocyte number and turnover and influence energy metabolism. Interestingly, a recently published study by Arner et al [42] demonstrated that lipolysis is an important predictor of future weight gain and impaired glucose metabolism. Hence, similar prospective studies using an in vivo approach (i.e.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of adipose tissue turnover in human metabolic health and disease

White

Ravussin

2018

Diabetologia

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White adipose tissue is a highly plastic organ and is an important regulator of whole-body metabolism and energy balance. The magnitude of adipose tissue mass is determined by dynamic changes in the synthesis and breakdown (i.e. turnover) of adipocytes and triacylglycerols (TGs). Obesity is a disorder characterised by excessive adiposity and is a risk factor for diseases, including the metabolic syndrome and type 2 diabetes. Adipose tissue expansion is necessary to accommodate chronic excess energy intake and is characterised by enlargement of existing adipocytes (hypertrophy) and by increase in pre-adipocyte and adipocyte numbers (hyperplasia). Evidence suggests that the manner of subcutaneous adipose expansion can influence metabolic health, as impaired adipogenesis, namely restricted hyperplasia, may lead to ectopic lipid deposition in the liver and skeletal muscle, contributing to the pathogenesis of obesity-related disorders. Despite the plausible role of adipose turnover in human health and pathology, little is known about the in vivo kinetics of adipose tissue components (both adipose cells and TGs). This is due, in part, to the slow turnover rate of adipose tissue and the complexity of directly labelling pathway precursors. This review provides a brief summary of findings derived from in vitro techniques, as well as an overview of two in vivo methods that are being implemented to assess the turnover of adipose cells and TGs. Finally, the role of adipose tissue turnover in metabolic health and disease is discussed.

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Weight Gain and Impaired Glucose Metabolism in Women Are Predicted by Inefficient Subcutaneous Fat Cell Lipolysis

Cited by 102 publications

References 58 publications

Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults

Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults

The novel non‐steroidal MR antagonist finerenone improves metabolic parameters in high‐fat diet‐fed mice and activates brown adipose tissue via AMPK‐ATGL pathway

Dynamics of adipose tissue turnover in human metabolic health and disease

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