Lipolysis defect in white adipose tissue and rapid weight regain

Research output: Contribution to journalArticle

Abstract

Weight regain after weight loss is a well-described phenomenon in both humans and animal models of obesity. Reduced energy expenditure and increased caloric intake are considered the main drivers of weight regain. We hypothesized that adipose tissue with obesity memory (OM) has a tissueautonomous lipolytic defect, allowing for increased efficiency of lipid storage. We utilized a mouse model of diet-induced obesity, which was subjected to 60% caloric restriction to achieve lean body weight, followed by a short period of high-fat diet (HFD) rechallenge. Agematched lean mice fed HFD for the first time were used as the control group. Upon rechallenge with HFD, mice with OM had higher respiratory exchange ratios than lean mice with no OM despite comparable body weight, suggesting higher utilization of glucose over fatty acid oxidation. White adipose tissue explants with OM had comparable lipolytic response after caloric restriction; however, reduced functional lipolytic response to norepinephrine was noted as early as 5 days after rechallenge with HFD and was accompanied by reduction in hormone-sensitive lipase serine phosphorylation. The relative lipolytic defect was associated with increased expression of inflammatory genes and a decrease in adrenergic receptor genes, most notably Adrb3. Taken together, white adipose tissue of lean mice with OM shows increased sensitization to HFD compared with white adipose tissue with no OM, rendering it resistant to catecholamineinduced lipolysis. This relative lipolytic defect is tissue-autonomous and could play a role in the rapid weight regain observed after weight loss.

Original languageEnglish (US)
Pages (from-to)E194-E199
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume317
Issue number2
DOIs
Publication statusPublished - Aug 2019

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Keywords

  • Adipose tissue
  • Lipolysis
  • Metabolic memory
  • Obesity
  • Weight regain

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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