Acyl-CoA Binding Protein in White and Brown Adipose Tissue Is Dispensable for Systemic Energy Metabolism in Mice

Acyl-CoA binding protein plays a vital role in lipid metabolism by mediating the intracellular flux and utilization of long-chain acyl-CoAs. We generated an adipocyte-wide ACBP knockout mouse and a brown adipose tissue-specific ACBP knockout mouse to investigate ACBP function in adipose tissue.

Male mice with conditional targeting of the Acbp gene in adipose tissue (Adipoq-Acbp^-/-) or brown adipose tissue (Ucp1-Acbp^-/-) were generated by crossing Acbp^flox/flox mice with transgenic mice expressing Cre recombinase under the control of the adiponectin (Adipoq-Cre) or uncoupling protein 1 (Ucp1-Cre) promoter, respectively. Systemic energy expenditure was assessed by indirect calorimetry. Body composition was examined using nuclear magnetic resonance. Primary brown and white preadipocytes were isolated to examine their ability to differentiate to mature adipocytes. Lipid composition of adipose tissues was examined by lipidomics. Global changes in gene expression in adipose tissues were examined by RNA sequencing. Tissue respiration was determined using high-resolution respirometry.

We demonstrate that loss of ACBP in adipose tissue does not affect body weight, fat and lean mass, food intake and systemic energy expenditure, even under cold stress. Global gene expression analysis shows only minor changes in gene expression, whereas lipidomic profiling reveals a subtle increase in acyl-carnitine levels in brown adipose tissue. Lipolytic activity in white adipose tissue as well as plasma glycerol, nonesterified fatty acid and triacylglycerol levels remained unaffected. In addition, no changes in mitochondrial respiration in BAT were observed.

Our findings suggest that ACBP is dispensable for adipose tissue function and systemic energy metabolism.