Fernanda Ornellas1, Isabele Bringhenti1, Brenda Akemi N F Mattos1, Carlos Alberto Mandarim-de-Lacerda2, Marcia Barbosa Aguila1. 1. Universidade do Estado do Rio de Janeiro, Centro Biomédico, Instituto de Biologia, Laboratório de Morfometria, Metabolismo e Doença Cardiovascular, Av 28 de Setembro 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil. 2. Universidade do Estado do Rio de Janeiro, Centro Biomédico, Instituto de Biologia, Laboratório de Morfometria, Metabolismo e Doença Cardiovascular, Av 28 de Setembro 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil. mandarim@uerj.br.
Abstract
PURPOSE: Studies demonstrated the influence of mother's obesity on offspring. However, the father is also related to programming the future generation. The study aimed to evaluate the effects of father's obesity upon white adipose tissue (WAT) remodeling, resulting in activation of signaling pathways and inflammation in male and female offspring. METHODS: Male C57BL/6 mice received control diet (lean father group; 17% energy from lipids) or high-fat diet (obese father group; 49% energy from lipids) for 8 weeks before mating. The mothers received control diet throughout the experiment. Mice were mated: lean mother and lean father, and lean mother and obese father. Offspring received control diet from weaning until 3 months of age when they were studied. RESULTS: In the offspring, father's obesity led to decreased QUICKI with impairment of the insulin signaling pathway in both sexes. In line with these findings, in white adipose tissue, male offspring demonstrated hypertrophied adipocytes, enhanced proinflammatory cytokines, overactivation of components of the local renin-angiotensin system (RAS) and extracellular signal-regulated kinase 1/2 (ERK1/2), and inhibition of peroxisome proliferator-activated receptors (alpha and gamma). CONCLUSIONS: We observed that father's obesity influences the offspring in adult life, with an impairment in insulin homeostasis, adipocyte remodeling, and adipose tissue overexpression of IL-6 and TNF-alpha in male offspring. The activation of local RAS and ERK1/2, a concomitant PPAR diminishing, and impairment in phosphorylation of AKT and IRS-1 could explain at least in part the findings regardless of the increase in body mass in the offspring.
PURPOSE: Studies demonstrated the influence of mother's obesity on offspring. However, the father is also related to programming the future generation. The study aimed to evaluate the effects of father's obesity upon white adipose tissue (WAT) remodeling, resulting in activation of signaling pathways and inflammation in male and female offspring. METHODS: Male C57BL/6 mice received control diet (lean father group; 17% energy from lipids) or high-fat diet (obese father group; 49% energy from lipids) for 8 weeks before mating. The mothers received control diet throughout the experiment. Mice were mated: lean mother and lean father, and lean mother and obese father. Offspring received control diet from weaning until 3 months of age when they were studied. RESULTS: In the offspring, father's obesity led to decreased QUICKI with impairment of the insulin signaling pathway in both sexes. In line with these findings, in white adipose tissue, male offspring demonstrated hypertrophied adipocytes, enhanced proinflammatory cytokines, overactivation of components of the local renin-angiotensin system (RAS) and extracellular signal-regulated kinase 1/2 (ERK1/2), and inhibition of peroxisome proliferator-activated receptors (alpha and gamma). CONCLUSIONS: We observed that father's obesity influences the offspring in adult life, with an impairment in insulin homeostasis, adipocyte remodeling, and adipose tissue overexpression of IL-6 and TNF-alpha in male offspring. The activation of local RAS and ERK1/2, a concomitant PPAR diminishing, and impairment in phosphorylation of AKT and IRS-1 could explain at least in part the findings regardless of the increase in body mass in the offspring.
Authors: Doris M Tham; Baby Martin-McNulty; Yi-xin Wang; Dennis W Wilson; Ronald Vergona; Mark E Sullivan; William Dole; John C Rutledge Journal: Physiol Genomics Date: 2002-10-02 Impact factor: 3.107
Authors: Jennifer E Cropley; Sally A Eaton; Alastair Aiken; Paul E Young; Eleni Giannoulatou; Joshua W K Ho; Michael E Buckland; Simon P Keam; Gyorgy Hutvagner; David T Humphreys; Katherine G Langley; Darren C Henstridge; David I K Martin; Mark A Febbraio; Catherine M Suter Journal: Mol Metab Date: 2016-06-23 Impact factor: 7.422