Adipose‐Selective Overexpression of CGI‐58 Does Not Alter Lipolysis or Protect Against Diet‐Induced Obesity

CGI‐58 is a lipid droplet protein that shares sequence similarity with lipases, but lacks a complete catalytic triad. CGI‐58 is highly expressed in adipose tissue and plays an important role in triacylglycerol catabolism; mutations in CGI‐58 cause excessive accumulation of triacylglycerols in non‐adipose tissues in humans. To study the role of CGI‐58 in adipose triacylglycerol metabolism, we generated transgenic mice overexpressing CGI‐58 selectively in adipose tissue, and studied lipolysis and changes in body weight and fat deposition in animals fed a high fat diet. Relative to wild‐type (Wt) mice, transgenic (Tg) mice had 6‐fold elevated protein levels of CGI‐58 in adipose tissue, but no significant differences in lipolysis after β‐adrenergic stimulation or fasting. Over 4 months, Wt and Tg mice fed a high fat diet showed similar increases in body weight and adipose tissue mass, as determined by DEXA. Histological examination and quantification of triacylglycerol levels revealed similar lipid infiltration in livers of Wt and Tg mice fed a high fat diet; Wt and Tg mice fed a low fat diet displayed minimal storage of triacylglycerols in liver. Since overexpression of CGI‐58 in adipose tissue had no effect on lipolysis and did not prevent diet‐induced obesity, we conclude that CGI‐58 is not a limiting factor for basal or stimulated lipolysis in adipose tissue.