Metabolic and structural changes in skeletal muscle that accompany obesity are often associated with the development of insulin resistance. The first events in the pathogenesis of this disorder are considered as an accumulation of lipids within skeletal muscle due to blunted muscle capacity to oxidize fatty acids. Fat infiltration is also associated with muscle fibre typology modification, decrease in muscle mass and impairments in muscle strength. Thus, as a result of obesity, mobility and quality of life are affected, and this is in part due to quantitative and qualitative impairments in skeletal muscle. In addition, the insulin resistance related to obesity results not only in defective insulin-stimulated glucose disposal but has also detrimental consequences on protein metabolism at the skeletal muscle level and whole-body level. This review highlights the involvement of fat accumulation and insulin resistance in metabolic disorders occurring in skeletal muscle during the development of obesity, and the impairments in the regulation of protein metabolism and protein turnover in the links between obesity, metabolic inflammation and insulin resistance.