Molecular and Hormonal Responses to Diet-Induced Insulin Resistance

This study determined the effect of 7 days of high-fat overfeeding on whole-body glycaemic control, glucose kinetics, skeletal muscle insulin signalling, and markers of skeletal muscle microvascular function in 15 healthy young individuals.

Fifteen healthy, young individuals underwent metabolic testing before and after 7 days of high-fat overfeeding. We determined whole-body glycaemic control, glucose kinetics, skeletal muscle insulin signalling, and markers of skeletal muscle microvascular function. Stable isotope tracers were used to assess the rate of appearance of glucose from the gut, liver glucose output and whole-body glucose disposal. Insulin signalling was determined by Western blotting of skeletal muscle tissue. Microvascular function was assessed through the use of quantitative immunofluorescence microscopy. These measurements were performed both postabsorptively and following the ingestion of 50 grams of glucose + 15 grams of protein.

15 healthy individuals were assessed before and after consuming a high-fat, high-energy diet for 7 days.

Participants underwent a 7 day high-fat, high-energy diet intervention with metabolic measurements before and after

Venous blood samples were obtained the day before and the day after the 7 day high-fat diet. Glucose was reported as mmol/L.

Venous blood samples were obtained the day before and the day after the 7 day high-fat diet. Insulin was reported as pmol/L.

Change in glucose kinetics (i.e., rate of appearance and disappearance) assessed using isotope tracers

Glucose kinetics were assessed the day before and the day after the 7 day high-fat diet. Data expressed as umol/kg/min.

AKT and AS160 phosphorylation was determined by Western blotting of skeletal muscle. Data are expressed as arbitrary units.

endothelial nitric oxide synthase was determined in terminal arterioles by quantitative immunofluorescence microscopy that was performed on sections of skeletal muscle tissue. Data presented as arbitrary units.

Intramuscular triglyceride content was determined by quantitative immunofluorescence microscopy that was performed on sections of skeletal muscle tissue. Data presented as arbitrary units.

Inclusion Criteria: Aged between 18 and 40 years Physically active Non-smoker Not taking any medication known to interfere with the study No history of cardiovascular disease or diabetes Weight stable for the last 6 months Exclusion Criteria: Outside of age range Sedentary Smoker Taking medication known to interfere with the study History of cardiovascular disease or diabetes Unstable weight within last 6 months

Parry SA, Turner MC, Woods RM, James LJ, Ferguson RA, Cocks M, Whytock KL, Strauss JA, Shepherd SO, Wagenmakers AJM, van Hall G, Hulston CJ. High-Fat Overfeeding Impairs Peripheral Glucose Metabolism and Muscle Microvascular eNOS Ser1177 Phosphorylation. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz018. doi: 10.1210/clinem/dgz018.