Medium-chain fatty acids attenuate agonist-stimulated lipolysis, mimicking the effects of starvation

Objective: To test the hypothesis that incorporation of medium-chain fatty acids (FAs) into adipocyte triglycerides alters intracellular lipolysis. Research Methods and Procedures: 3T3-L1 adipocytes were pretreated with octanoate for various incubation periods. After the removal of exogenous FAs, cells were incubated with different lipolytic agonists. To determine the effects on lipolysis, we measured the following: the release of glycerol and FAs, lipase activity, protein levels of hormone-sensitive lipase (HSL), and perilipin A; translocation of HSL; phosphorylation of perilipin A; and levels of cellular adenosine triphosphate, cyclic adenosine monophosphate, and H2O2. To compare the effects of starvation with those caused by octanoate pretreatment, we measured glycerol release and H2O2 generation in rat adipocytes of starved donors. Results: Pretreatment of adipocytes with octanoate in vitro increased basal lipolysis but decreased the cellular response for agonists. The same effects were seen in starvation in vivo. Preincubation with octanoate for 48 hours did not affect basal lipase activity, HSL, and perilipin protein levels, but it reduced agonist-stimulated perilipin phosphorylation and HSL translocation toward fat droplets. This was associated with a reduction in basal cellular adenosine triphosphate levels and agonist-stimulated cyclic adenosine monophosphate generation. Starvation and octanoate pretreatment both increased intracellular H2O2 concentrations, which might also contribute to the inhibition on agonist-stimulated lipolysis. Discussion: Pretreatment with octanoate seems to induce changes in adipocyte lipolysis in a pattern mimicking the effects of starvation. Such changes could contribute, in part, to weight loss in animals and humans associated with dietary medium-chain FAs.