Betydelsen av fettsyror för ektopisk fettinlagring och muskelhypertrofi: metabola och molekylära studier

Tidsperiod: 2015-01-01 till 2017-12-31

Projektledare: Ulf Risérus

Medarbetare: Håkan Ahlström, Ingrid Dahlman

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 3 000 000 SEK

Factors influencing body fat accumulation are poorly understood. Individuals that deposit fat in the liver, muscle and pancreas (ectopic fat) without increasing lean tissue (sarcopenic obesity) are prone to insulin resistance and metabolic disease. Fatty acids play key roles in fat metabolism since they are energy mediators, signaling molecules and gene regulators. In our recent overfeeding trial, polyunsaturated fatty acids prevented ectopic fat storage and increased lean tissue, whereas saturated fat (palmitate) had the opposite effects. The mechanisms are however not fully understood. We aim to investigate fatty-acid specific effects on lean tissue mass and ectopic fat accumulation in response to weight gain (overfeeding) and weight loss (energy restriction), and evaluate the molecular response in skeletal muscle and adipose tissue. Transcriptomics, epigenomics and metabolomics will be applied to explore ?global? molecular and metabolic effects, and we will quantify genes and proteins involved in fat metabolism, insulin signaling, and protein synthesis. Fat cell size and number will be determined during overfeeding and linked to changes in insulin sensitivity. Fatty acid uptake in key tissues will be determined by functional imaging (PET-MRI). This study could provide new insights in the FA-dependent effects on body composition, and identify molecular and metabolic actions of importance for lean tissue changes, ectopic fat accumulation and insulin resistance.