Can the health benefits of a walking-based exercise programme be enhanced by co-ingestion of a lipid lowering drug?

Future Physiology 2019 (Liverpool, UK) (2019) Proc Physiol Soc 45, PC23

Poster Communications: Can the health benefits of a walking-based exercise programme be enhanced by co-ingestion of a lipid lowering drug?

J. Barrett1

1. Sport and Exercise Science, Liverpool John Moores University, Liverpool, United Kingdom.

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Although insulin resistance in obesity and T2D is associated with IMTG accumulation in muscle, endurance training is associated with larger IMTG stores, but with high insulin sensitivity in a phenomenon termed the “athlete’s paradox”. Because endurance training increases muscle oxidative capacity and the utilisation of IMTG as a fuel during exercise, it is believed that the ability to utilise IMTG during exercise is mechanistically important to preserve insulin sensitivity alongside elevated IMTG storage. High rates of IMTG utilisation allows regular turnover if the IMTG pool, leading to reduced accumulation of lipid metabolites such as DAGs and ceramides. These lipid metabolites reduce the insulin-induced activation of IRS-1 and Akt, respectively. Thus, preventing activation of the insulin signalling cascade, GLUT4 translocation and glucose uptake into skeletal muscle. Acute use of anti-lipolytic agents has shown to Improve insulin sensitivity and glucose control, but fail to maintain these beneficial effects long-term. Regular exercise training in lean, sedentary individuals is effective at increasing IMTG utilisation paired with improvements in insulin sensitivity. Low intensity brisk walking is well tolerated by overweight/obese individuals however walking interventions result in little or no improvements in insulin sensitivity. Since Acipimox ingestion enhances muscle glycogen utilisation, a combined intervention with regular brisk walking could effectively stimulate IMTG utilisation and enhance the benefits of a walking based exercise program in obese individuals. Methods: 34 sedentary, overweight/obese people (aged 25-50 years, BMI >28 kg.m-2) with prediabetes will be recruited and split into two groups; exercise (EX), and exercise plus Acipimox ingestion (EX+ACIP). Participants attend 3 supervised walking exercise per week for 12 weeks. Body composition, maximal aerobic fitness (VO2 max), liver fat via MRI and skeletal muscle insulin sensitivity via hyperinsulinemic euglyceamic clamp will be measured pre- and post-exercise intervention. Hypothesis and Implications: It is hypothesised that an exercise programme of steady walking will have larger effects on insulin sensitivity and glycaemic control when combined with Acipimox prior to each exercise session in individuals with pre-diabetes.



Where applicable, experiments conform with Society ethical requirements.

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