title: Obesity--a disease with many aetiologies disguised in the same oversized phenotype: has the overeating theory failed?
abstract: Evolution has led to metabolic thrift in humans--a genetic heritage that, when exposed to the modern 'obesogenic' milieu with energy-dense food and a sedentary lifestyle, predisposes to obesity. The current paradigm that overeating of easily digestible carbohydrates and the resulting imbalance between energy in and out as the cause of overweight has recently been challenged. Indeed, studies suggest that the host response to various nutrients contributes to overeating and fat accumulation. Alterations in neurotransmitter functions, changes in the epigenome, dysbiosis of gut microbiota and effects of specific nutrients (or lack of such nutrients) on mitochondrial function and signalling pathways may promote fat accumulation independent of calories. Whereas nutrients that stimulate generation of uric acid (such as fructose and purine-rich food) cause insulin resistance and fat accumulation, other nutrients (such as antioxidants, plant food, probiotics, nuts, soy and omega-3) counteract the negative effects of a calorie-rich diet by salutary effects on mitochondrial biogenesis. Thus, the specific metabolic effects of different nutrients may be more important than its total energy content. By studying the impact of nutrients on mitochondrial health, as well as the trans-generational impact of nutrients during fetal life, and how specific bacterial species correlate with fat mass accumulation, new dietary targets for obesity management may emerge. Overeating and overshooting of calories could to a large extent represent a symptom rather than a cause of obesity; therefore, hypocaloric diets should probably not be the main, and certainly not the only, focus for treatment of the obese patient.
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
mesh_terms: D004032:Diet / Q000009:adverse effects*; D006801:Humans; D006963:Hyperphagia / Q000503:physiopathology*; D024821:Metabolic Syndrome / Q000209:etiology*; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D010641:Phenotype
keywords: epigenome; gut microbiota; insulin resistance; mitochondria; obesity