Impact of moderate exercise on fatty acid oxidation in pancreatic β-cells and skeletal muscle

Abstract

Fatty acids (FA) play a crucial role in glycaemia regulation in healthy and metabolic disorders conditions through various mechanisms. FA oxidation is one of the processes involved in lipid metabolism and can be modulated by exercise. Nowadays, physical activity is known to be an effective strategy for the prevention and treatment of Type 2 Diabetes. Moreover, its intensity, its duration, the sex-gender, the prandial state, exerkines… are as many parameters that can influence glycaemic control. However, the widely debated question is to determine the best type of exercise for patients with metabolic disorders. In this review, we will discuss the impact of exercise intensity, especially moderate activity, on glycaemic control by focussing on FA oxidation in pancreatic β-cells and skeletal muscle. Finally, thanks to all the recent data, we will determine whether moderate physical activity is a good therapeutic strategy and if FA oxidation represents a target of interest to treat diabetic, obese and insulin-resistant patients.

Keywords: FA oxidation; Moderate exercise; Pancreatic beta cell; Skeletal muscle.

Fig. 1

Mechanisms of Fatty acids and glucose mitochondrial β-oxidation. ATP and CO₂ are produced by cell from glucose and FA pathways. Focussing on lipid metabolism, FAs enter the cell via specific transporters (CD36/FAT, FABP) or are provided from TAG present in the cytosol. Before entering inside mitochondria, FAs are activated in FA-Acyl CoA form by ACS enzyme. After that, CPT1/2 convert FA-Acyl CoA in Acyl-CoA and β-oxidation is also performed to produce Acetyl-CoA. Finally, this latter is used by the TCA cycle to produce ATP and CO₂ necessary for cell physiology. Malonyl-CoA is a key regulator of this mechanism inhibiting CPT1 and consequently the transfer of FA-AcylCoA into the mitochondria. Malonyl-CoA is produced by ACC and catabolized by MCD. ATP Adenosine Triphosphate, CO₂ Dioxide carbon, FA Fatty acid, CD36 Cluster of differentiation 36, FAT Fatty acid transporter protein, FABP Fatty acid binding protein, FA-Acyl CoA Fatty acid-Acyl Coenzyme A, TAG triacylglycerol, ACS Acyl-CoA synthetases, CPT1/2 Carnitine palmitoyl transferase 1 and 2, TCA Tricarboxylic acid, Malonyl-CoA Malonyl-Coenzyme A, ACC Acetyl-Coenzyme A carboxylase, MCD Malonyl coenzyme A decarboxylase

Fig. 2

Impact of moderate exercise on pancreatic β-cell in patients with metabolic disorders: focus on FA oxidation, β-cell function and survival. In β-cells, FA oxidation is decreased in people with metabolic disorders. Moreover, physical activity can improve their metabolic control. However, moderate exercise does not allow to restore physiological FA oxidation despite an improvement of β-cell function and survival in diabetic patients. Thus, others mechanisms are involved, such as skeletal muscle-secreted myokines and lipid metabolism, which are described to have exercise-induced beneficial effects. FA Fatty acid

Fig. 3

Impact of moderate exercise in skeletal muscle of patients with metabolic disorders: focus on FA oxidation, insulin sensitivity and glucose uptake. In skeletal muscle, FA oxidation and glycaemic control are altered in people with metabolic disorders. Exercise improves peripheral insulin sensitivity in T2D patients and has a beneficial effect on insulin resistance. However, only high intensive exercise improves metabolic control in skeletal muscle. This beneficial effect is not related to its impact on FA oxidation but dependent to skeletal muscle-secreted myokines, plasmatic FA level and to the activation of specific Gq-GPCRs. FA Fatty acid, Gq-GPCRs subunit Gq-G-coupled FA receptors, AMPK Adenosin monophosphate-activated protein kinase