Increasing intracellular calcium in adipocytes increases fatty acid oxidation via the activation of AMP‐activated protein kinase

Abstract

Increased dietary calcium intake is associated with reduced adiposity in humans. We hypothesized that increased intracellular Ca++ would augment fatty oxidation in 3T3‐L1 adipocytes in an AMP‐activated protein kinase (AMPK)‐dependent manner. Adipocytes were grown under euglycemic (EG) or hyperglycemic (HG) conditions and treated with or without calcium ionophores (4x10‐6 M A23187 and 4x10‐6 M Ionomycin, [AI]). After 15–60 min, AI increased intracellular Ca++ concentrations by 250% (P<0.001) and 150% (P<0.05), in EG and HG cells respectively, vs. controls. P‐AMPK and P‐Acetyl CoA carboxylase protein abundance was up regulated by AI in a time‐dependent manner. This was associated with increased 14C‐palmitate oxidation under EG (267%, P<0.001) or HG (200%, P<0.02) vs. the controls. However, the AMPK inhibitor, adenosine 9‐beta‐d‐arabinofuranoside (araA), attenuated the AI‐induced increase in fatty acid oxidation (P<0.01) under both conditions. HG results in insulin resistance and impaired glucose uptake in adipocytes. Compared to the control, AI improved this glucose uptake by 210% (P<0.01), even in the presence of araA (180%, P<0.05). These data indicate that intracellular Ca++ is a significant determinate of fatty acid oxidation via the control of AMPK activity. In contrast, the ability of increased intracellular Ca++ to enhance glucose uptake in HG conditions is independent of the activation of AMPK.