Elsevier

Metabolism

Volume 56, Issue 12, December 2007, Pages 1719-1728
Metabolism

High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle

https://doi.org/10.1016/j.metabol.2007.07.017Get rights and content

Abstract

A single bout of exercise increases the rate of muscle glucose transport (GT) by both insulin-independent and insulin-dependent mechanisms. The purpose of this study was to determine whether high-fat diet (HFD) feeding interferes with the metabolic activation induced by moderate-intensity endurance exercise. Rats were fed an HFD or control diet (CD) for 4 weeks and then exercised on a treadmill for 1 hour (19 m/min, 15% incline). Insulin-independent GT was markedly higher in soleus muscle dissected immediately after exercise than in muscle dissected from sedentary rats in both dietary groups, but insulin-independent GT was 25% lower in HFD-fed than in CD-fed rats. Insulin-dependent GT in the presence of submaximally effective concentration of insulin (0.9 nmol/L) was also higher in both dietary groups in muscle dissected 2 hours after exercise, but was 25% lower in HFD-fed than in CD-fed rats. Exercise-induced activation of 5′adenosine monophosphate–activated protein kinase, a signaling intermediary leading to insulin-independent GT and regulating insulin sensitivity, was correspondingly blunted in the HFD group. High-fat diet did not affect glucose transporter 4 content or insulin-stimulated Akt phosphorylation. Our findings provide evidence that an HFD impairs the effects of short-term endurance exercise on glucose metabolism and that exercise does not fully compensate for HFD-induced insulin resistance in skeletal muscle. Although the underlying mechanism is unclear, reduced 5′adenosine monophosphate–activated protein kinase activation during exercise may play a role.

Introduction

Physical exercise has profound effects on glucose metabolism in contracting skeletal muscle. Exercise activates glucose transport (GT) in skeletal muscle by inducing translocation of glucose transporter 4 (GLUT4) to the cell surface by insulin-independent and insulin-dependent mechanisms (reviewed in Hayashi et al [1]). The activity of insulin-independent GT is markedly enhanced during exercise; and this effect wears off within several hours after exercise, when the postexercise increase in insulin sensitivity that leads to insulin-dependent GT becomes prominent. Wallberg-Henriksson et al [2] showed in isolated rat skeletal muscle that the rate of insulin-independent GT is maximal immediately after exercise, whereas the postexercise increase in insulin sensitivity becomes detectable 3 hours after exercise. Correspondingly, Price et al [3] showed in human muscle that postexercise glycogen repletion occurs in an insulin-independent manner for about 1 hour after exercise, after which insulin-dependent glycogen repletion becomes significant. These exercise-stimulated mechanisms form the basis of practices to prevent individuals from developing glucose intolerance and to improve glycemic control in patients with type 2 diabetes mellitus.

It is of interest to know whether exercise-stimulated GT, including both the insulin-independent and insulin-dependent components, is normal in the state of insulin resistance. Although numerous studies have shown that a high-fat diet (HFD) causes insulin resistance in muscles at rest, it is unknown whether an HFD interferes with the short-term stimulatory effect of exercise on insulin sensitivity. Only one study has addressed this topic and demonstrated that the postexercise increase in muscle insulin sensitivity is abolished completely in HFD-fed rats [4]. In that study, however, insulin-dependent GT was measured before the insulin-independent glucose uptake wore off (its activity was still 160% higher than the basal uptake), indicating that the net effect of exercise on insulin sensitivity was substantially underestimated because of residual glucose uptake activity. There is considerable controversy over whether an HFD alters the effects of short-term exercise on insulin-independent GT. Most investigators have reported about 50% reduction in the rate of muscle GT stimulated by exercise [5], [6], [7] and electrical stimulation [6], [8], [9] in HFD-fed rodents, although others did not find these effects [4], [10]. Moreover, some studies have shown that the reduction in insulin-independent GT was not associated with decreased muscle GLUT4 content [5], [6]; but a conflicting result was also reported [8]. Although Hansen et al [9] showed that impairment of the exercise-stimulated GT is associated with decreased GLUT4 translocation to the cell surface, the responsible signaling mechanism remains to be elucidated.

The purposes of our present study were to determine how HFD affects insulin-independent and insulin-dependent GT activated by a single bout of endurance exercise and to explore the underlying mechanism that leads to the change in exercise-stimulated glucose utilization. We found that both components of exercise-induced GT were impaired by an HFD and that these changes were accompanied by a decrease in 5′adenosine monophosphate (AMP)–activated protein kinase (AMPK) activation in skeletal muscle of rats fed an HFD for 4 weeks.

Section snippets

Animals and diets

Male Wistar rats at the time of weaning were purchased from Clea Japan (Tokyo, Japan). Animals were fed either control diet (CD) (MF; 3.6 kcal/g, 12% kcal fat, source: soybean; Oriental Yeast, Tokyo, Japan) or HFD (D12493; 5.2 kcal/g, 60% kcal fat, source: soybean/lard; Research Diets, New Brunswick, NJ) for 4 weeks. All animal experiments were approved by the Animal Research Committee, Graduate School of Medicine, Kyoto University.

Exercise and muscle sampling

The rats were accustomed to a rodent treadmill (Muromachi

Metabolic parameters in rats fed the CD and HFD

Table 1 summarizes the basic characteristics of the CD- and HFD-fed rats (Table 1). Rats fed the HFD for 4 weeks were slightly heavier and had higher plasma concentrations of glucose, insulin, triglycerides, and leptin than did CD-fed rats.

HFD increases IMCL in soleus

We analyzed the influence of HFD on IMCL concentration by ORO staining (Fig. 1A-B). Muscle fiber type was determined by myofibrillar ATPase histochemical staining (Fig. 1C-F). The fiber type proportions did not differ significantly between CD-fed and HFD-fed

Discussion

Endurance exercise has long been advocated as beneficial for patients with insulin resistance associated with type 2 diabetes mellitus and obesity. This is based partly on the observation that, even in people with insulin resistance, endurance exercise stimulates muscle glucose uptake in skeletal muscle by 2 distinct mechanisms: one insulin independent and one insulin dependent (reviewed in Hayashi et al [1]). Reversal of the short-term increase in GT after cessation of contractile activity is

Acknowledgments

We thank Takao Shirai, Kyoto University, for technical suggestions and Yoko Koyama and Kaoru Ijiri for secretarial assistance. We also thank the Radioisotope Research Center of Kyoto University for instrumental support in the radioisotope experiments. This work was supported by a research grant from the Japan Society for the Promotion of Science (to Tatsuya Hayashi). Taro Toyoda was supported by the Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists.

References (50)

  • D.H. Han et al.

    Insulin resistance of muscle glucose transport in rats fed a high-fat diet: a reevaluation

    Diabetes

    (1997)
  • P.T. Fueger et al.

    Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high-fat–fed C57BL/6J mice

    Diabetes

    (2004)
  • X. Han et al.

    Effect of diet on insulin- and contraction-mediated glucose transport and uptake in rat muscle

    Am J Physiol

    (1995)
  • M. Kusunoki et al.

    Muscle glucose uptake during and after exercise is normal in insulin-resistant rats

    Am J Physiol

    (1993)
  • T. Toyoda et al.

    Possible involvement of the alpha1 isoform of 5AMP-activated protein kinase in oxidative stress–stimulated glucose transport in skeletal muscle

    Am J Physiol Endocrinol Metab

    (2004)
  • T. Toyoda et al.

    Low-intensity contraction activates the alpha1-isoform of 5′-AMP–activated protein kinase in rat skeletal muscle

    Am J Physiol Endocrinol Metab

    (2006)
  • L. Miyamoto et al.

    Effect of acute activation of 5′-AMP–activated protein kinase on glycogen regulation in isolated rat skeletal muscle

    J Appl Physiol

    (2007)
  • M.H. Brooke et al.

    Muscle fiber types: how many and what kind?

    Arch Neurol

    (1970)
  • T. Hashimoto et al.

    Immunohistochemical analysis of MCT1, MCT2 and MCT4 expression in rat plantaris muscle

    J Physiol

    (2005)
  • B.H. Goodpaster et al.

    Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes

    J Clin Endocrinol Metab

    (2001)
  • T. Tanaka et al.

    Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification

    Diabetes

    (2005)
  • T. Hayashi et al.

    Evidence for 5′AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport

    Diabetes

    (1998)
  • E.J. Kurth-Kraczek et al.

    5′AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle

    Diabetes

    (1999)
  • J.S. Fisher et al.

    Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin

    Am J Physiol Endocrinol Metab

    (2002)
  • J. Kim et al.

    Postcontraction insulin sensitivity: relationship with contraction protocol, glycogen concentration, and 5′AMP-activated protein kinase phosphorylation

    J Appl Physiol

    (2004)
  • Cited by (66)

    • Lycium barbarum polysaccharides ameliorates renal injury and inflammatory reaction in alloxan-induced diabetic nephropathy rabbits

      2016, Life Sciences
      Citation Excerpt :

      Previous studies have reported that the early stage symptoms of diabetic nephropathy could not be observed until 8–12 weeks after a single dose (100–160 mg/kg) ALX injection in the rabbit model [42–44]. The high fat diet was reported to development insulin resistance in mammals [45–47]. Moreover, our experiment confirmed that 100 mg/kg ALX injection combined with high fat diet after the DM model had succeeded for 2 weeks was more available to establish diabetic nephropathy in rabbits.

    View all citing articles on Scopus
    View full text