Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective

Abstract

Although the prevalence of obesity is increasing in most countries, partially due to ubiquitous exposure to energy dense foods, not everyone exposed to the current obesogenic environment shows unhealthy weight gain. This suggests that there are marked differences in genetic factors that increase vulnerability for excess weight gain. Indeed, evidence suggests that 40 to 70% of variance in unhealthy weight gain can be attributed to individual genetic variations. Moreover, emerging data imply that genetic vulnerability factors interact with environment risk, which is referred to as an epigenetic process.Whereas most scholars consider obesity to be a disorder that results from the interaction between lifestyle and genetic factors, its origin is complex, poorly understood, and extent treatments are typically ineffective. Like any other aspect of science, our knowledge about the genetic basis of obesity is under constant revision. The current paper provides a review on the origins, mechanisms, evolutionary explanation, prevention and treatment based on genotyping.

A novel MC4R deletion coexisting with FTO and MC1R gene variants, causes severe early onset obesity

“…15 Its rising prevalence and complex pathogenesis could be attributed to the interplay between dietary, environmental and genetic factors. 16 This case report is a concrete example of the interaction between adipose regulatory genes and an unhealthy lifestyle resulting in morbid obesity. of excessive growth hormone (GH) secretion due to MC4R deficiency, GH pulsatility is maintained, suggesting a role for MC4R in controlling hypothalamic somatostatinergic tone.…”

Fisiopatología de la obesidad: Perspectiva actual

“…En esta actualización nos centraremos en la obesidad poligénica, no en la obesidad monogénica, como puede ser una mutación en el gen que codifica la leptina o su receptor, o sindrómica, como un Prader Willi o Bardet-Biedl 7 . Atendiendo a estos dos criterios podemos parafrasear a Ortega y Gasset en sus Meditaciones del Quijote: "yo soy yo (genética) y mis circunstancias (epigenética/ambiente)", estableciendo un marco conceptual más amplio con el que trabajar alejado de la clásica concepción sedentarismo y sobrealimentación como factores causales que nos ha acompañado durante 2.500 años 8 .…”

Obesidad y genética

“…Estos genes podrían haber sido seleccionados naturalmente con la evolución al permiti r, en ti empos de hambruna, la supervivencia de quienes poseen genes 'ahorradores' (5) . La complejidad de los mecanismos que intervienen en la regulación del peso corporal y hábitos alimentarios se refl eja también en la infl uencia de 'factores epigenéti cos', elementos regulatorios que, sin alterar el ADN, infl uyen en la expresión de los genes, como son la meti lación del ADN, aceti lación de las histonas y, como descubrimiento más reciente, los microRNA o miR y otros mecanismos epigenéti cos (6,7) .…”