Physical exercise improves low cardiorespiratory fitness associated with intramyocellular lipids in patients with metabolic syndrome

Abstract

I n recent years, factors such as the westernization of dietary habits and an increasingly sedentary life style have led to a striking increase in the number of people with metabolic syndrome (MetS). Obesity is situated at the origin of the MetS and causes insulin resistance. 1 Insulin resistance itself is a characteristic feature of type 2 diabetes and obesity. The etiology of insulin resistance is multifactorial and involves both genetic and environmental factors. 2 Several lines of evidence have been provided in support of the hypothesis that intramyocellular lipids (IMCLs) and intrahepatic lipids (IHLs), as assessed non-invasively by localized 1 H-magnetic resonance spectroscopy, are associated with reduced-insulin action in both obese and non-obese subjects. 2,3 In addition, high IMCL levels are associated with the impairment of early insulin signal transduction in specimens obtained from muscle biopsies, because IMCLs and related intracellular substances, such as diacylglycerol or protein kinase C, are important regulators of insulin resistance in skeletal muscle. 4 Insulin-resistant individuals have a reduced rate of fat oxidation, compared with normal, insulin-sensitive individuals, and thus, the decreased mitochondrial fat oxidative capacity could lead to an increase in the intracellular fat content. 5 It has also been reported that IHL accumulation is associated with impaired hepatic glucose metabolism. The suppressive effect of insulin on hepatic glucose production was shown to be negatively correlated with the IHL content in both healthy subjects and patients with type 2 diabetes. 4 DeFronzo 5 stated that the accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, b-cells and arterial tissues contributes to insulin resistance, b-cell dysfunction and accelerated atherosclerosis, respectively, in individuals with type 2 diabetes. Given the close relationship between IHLs and insulin sensitivity, Haufe et al. 2 investigated the relationship between IHLs and both fitness and insulin sensitivity, and concluded that the positive effect of increased cardiorespiratory fitness (CRF) on insulin sensitivity in overweight and obese subjects seems to be indirectly mediated by IHL content rather than the amount of total, visceral and subcutaneous fat. Potential mechanisms linking CRF and IHLs may include factors that regulate hepatic lipid oxidation. Substrate oxidation is tightly coupled to mitochondrial oxidation capacity. Mitochondria occupy nearly 18% of the hepatocyte volume, and their function, a strong determinant of fitness, could conceivably affect hepatic lipid oxidation. 2 Low CRF is a predictor of all-cause mortality in patients with type 2 diabetes and in healthy people. 6 Sawada et al. 7 investigated the relationship between long-term trends in CRF and the incidence of type 2 diabetes in a cohort of 41 787 non-diabetic Japanese men who completed annual health checkups and fitness tests for the estimation of maximal oxygen uptake over 7 years. T...

Dietary Energy Partition: The Central Role of Glucose

“…This approach is not always feasible, since obesity is syndromic with cardiovascular disease and problems of mobility [ 221 ] and, despite numerous claims on the contrary, exercise it not sufficient to revert the damages of an established MS [ 222 ], and may not improve the health status [ 223 ]. However, well dosed exercise may provide benefits to mild cases and young patients [ 224 ]. In addition, the effectiveness of exercise is also limited from the point of view of energy: limited duration, limited proportion of increase in overall energy consumed, consequences in the availability and transport of oxygen and products of substrate oxidation.…”

Combination of bofutsushosan (Kampo medicine) and voluntary exercise improves insulin sensitivity in Otsuka Long-Evans Tokushima fatty rats

“…Continued moderate physical exercise reduces visceral fat, improves insulin resistance, and is useful for preventing and treating metabolic syndrome . It is well known that voluntary exercise can improve peripheral insulin action due to increased insulin‐signaling intermediaries .…”