Jackisch L, Murphy AM, Kumar S, et al. - Researchers ascertained if endoplasmic reticulum (ER) stress contributes to the development of mitochondrial inefficiency in human adipocytes from lean and obese candidates. Human differentiated adipocytes from Chub-S7 cell line and primary abdominal subcutaneous adipocytes from lean and obese candidates have been treated with tunicamycin to induce ER stress. ER stress in a model adipocyte system led to increased respiratory efficiency in a concentration and time-dependent manner. It corresponded with mitochondrial inefficiency and reduced MMP, emphasizing dysfunctional mitochondrial formation. Such human data indicate that adipocyte mitochondrial inefficiency is driven by ER stress and exacerbated in obesity. Nutrient excess–induced ER stress contributes to mitochondrial dysfunction, which can thus shift lipid deposition ectopically and can have further implications on the development of associated metabolic disorders.