title: Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation.
abstract: The consumption of Western diets, high in sugar and saturated fat, is a crucial contributor to the alarming incidence of obesity and its associated morbidities. These diets have been reported to induce an inflammatory response in the hypothalamus, which promotes the development of central leptin resistance and obesity. This inflammatory signalling involves dynamic changes in the expression and activity of several mediators of the innate immune system, including toll-like receptor 4, IκB kinase-β/nuclear factor-κB, c-Jun N-terminal kinase, suppressor of cytokine signalling 3 and pro-inflammatory cytokines, as well as the induction of endoplasmic reticulum stress and autophagy defect. Although the exact cellular mechanisms remain incompletely understood, recent evidence suggests that the inflammatory response is at least mediated by interactions between neurons and non-neuronal cells such as microglia and astrocytes. Current evidence of the contribution of each inflammatory mediator to leptin resistance and diet-induced obesity (DIO), including their reciprocal interactions and cell-type-specific effects, is reviewed and integrated in a conceptual model. Based upon this model and pharmacological intervention studies, several inflammatory mediators are proposed to be promising therapeutic targets for the treatment of DIO.
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: K C G
authors.initials: KC
authors.lastname: de Git
authors.forename: R A H
authors.initials: RA
authors.lastname: Adan
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004734:Energy Metabolism; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress; D051381:Rats; D015398:Signal Transduction
chemical_list: D020738:Leptin
keywords: Diet-induced obesity; hypothalamus; inflammation; leptin resistance