Effects of Obesity on Autophagy and mTORC1 Signalling in Skeletal Muscle

As skeletal muscle is a major contributor to basal metabolic rate and glucose control, increasing the quality of skeletal muscle in those living with obesity could improve the long-term success of subsequent weight loss programs. There are two main activities which are often recommended to improve skeletal muscle quality, resistance exercise (i.e. weightlifting) and adequate protein intake, however, recent research has suggested that individuals living with obesity do not respond as well to these activities as a non-obese person. This research project aims to investigate if certain processes within muscle cells, which regulate muscle size and quality, are reduced in people living with obesity following a single session of resistance exercise and a protein-rich drink. This will hopefully identify processes we can target specifically to improve skeletal muscle quality. The project involves participants attending the lab and completing a session of single-leg resistance exercise and ingesting a protein drink. Before and after this the investigators will take a number of blood samples and small pieces of muscle from each thigh to understand how muscle reacts to exercise/feeding and whether this differs between individuals with and without obesity. Following the visit investigators will the conduct a variety of laboratory analysis on these samples to understand the responses. Overall, this project has the potential to help design future programmes which can improve skeletal muscle quality in those living with obesity, improving general health and increasing success of weight loss interventions.

To date, the acute effects anabolic stimulation by resistance exercise and protein ingestion in individuals with obesity have been shown to be blunted. However, the mechanisms responsible for this have scarcely been investigated. We intend to build on current evidence by identifying what causes this blunted response to anabolic stimulation in individuals with obesity.

This project aims to determine whether individuals with obesity exhibit differential mTORC1-lysosomal translocation in response to anabolic signaling following a single bout of resistance exercise combined with protein ingestion.

Inclusion criteria

• Age - 18-45yrs
• BMI - 18.5-24.9kg/m2 OR >28kg/m2 (self-declaration, or calculated by research team based on height and weight)
• Weight Stable i.e. no change in weight of more than 5% in previous 6 months
• Meeting UK Physical activity guidelines (150 mins moderate or 75 mins vigorous activity/wk)
• Not involved in structured exercise training in previous 6 months
• No other diagnosed metabolic or neuromuscular conditions (self-declaration)

Exclusion criteria

• Currently using anti-diabetes medication (insulin, metformin, sulphonylureas, meglitinides, thiazolidinediones, DPP- 4 inhibitors, GLP-1 inhibitors).
• Currently taking cholesterol lowering medications (statins)
• Currently engaged in active weight loss programmes or using weight loss medication
• Chronic kidney disease (moderate to severe reduction in kidney function), defined as eGFR <30 ml/min/1.73m2 identified by self declaration.
• Pregnant or breast feeding
• Currently using anti-coagulation medication
• Hypothyroidism
• Type 1 diabetes
• Current or recent weakness/injury to either leg that may affect muscle function or ability to exercise
• Current gastrointestinal issue/condition that may affect digestion and absorption of protein drink
• Individuals who follow a vegan diet or have intolerance/allergies to Whey protein.
• Previous adverse reaction to local anaethetic (lidocaine or marcaine).