Endocrine Abstracts

Weight regain after weight loss is a well described-phenomena in both humans and animal models of obesity and thought to be related to reduced energy expenditure and increased food intake. Reduced lipolysis in white adipose tissue has been described in obesity. We hypothesized that lipolytic defect in adipose tissue in the obese state persists after weight loss increasing efficiency of lipid storing and promotes weight regain. We utilized a mouse model of obesity memory (OM): C57BL/6 mice with diet induced obesity were subjected to 60% caloric restriction to achieve lean body weight, followed by a short period of high fat diet (HFD) re-challenge. Age-matched lean mice without OM which were fed HFD for the first time were used as control. Upon re-challenge with HFD, mice with OM had rapid weight gain compared to the control group. Despite comparable body weight and lean body mass, mice with OM showed higher respiratory exchange ratio than control mice, suggesting higher glucose rather than fatty acid oxidation. In ex vivo lipolysis assay 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 re-challenge with HFD accompanied by reduction in HSL serine phosphorylation after norepinephrine stimuli. The relative lipolytic defect was associated with increased expression of inflammatory genes, and a decrease in beta adrenergic receptor genes, most notably adrb3 compared to the control group. Taken together, white adipose tissue of lean mice with OM shows increased sensitization to HFD compared to white adipose tissue with no OM, rendering it relatively resistant to catecholamine induced-lipolysis. This lipolytic defect associated with OM is tissue-autonomous and could play a role in the rapid weight regain observed after weight loss.