RT Journal Article
T1 Intergenerational Influence of Paternal Obesity on Metabolic and Reproductive Health Parameters of the Offspring: Male-Preferential Impact and Involvement of Kiss1-Mediated Pathways.
A1 Sanchez-Garrido, Miguel Angel
A1 Ruiz-Pino, Francisco
A1 Velasco, Inmaculada
A1 Barroso, Alexia
A1 Fernandois, Daniela
A1 Heras, Violeta
A1 Manfredi-Lozano, Maria
A1 Vazquez, Maria Jesus
A1 Castellano, Juan Manuel
A1 Roa, Juan
A1 Pinilla, Leonor
A1 Tena-Sempere, Manuel
K1 Animals
K1 Fathers
K1 Kisspeptins
K1 Obesity
AB Obesity and its comorbidities are reaching epidemic proportions worldwide. Maternal obesity is known to predispose the offspring to metabolic disorders, independently of genetic inheritance. This intergenerational transmission has also been suggested for paternal obesity, with a potential negative impact on the metabolic and, eventually, reproductive health of the offspring, likely via epigenetic changes in spermatozoa. However, the neuroendocrine component of such phenomenon and whether paternal obesity sensitizes the offspring to the disturbances induced by high-fat diet (HFD) remain poorly defined. We report in this work the metabolic and reproductive impact of HFD in the offspring from obese fathers, with attention to potential sex differences and alterations of hypothalamic Kiss1 system. Lean and obese male rats were mated with lean virgin female rats; male and female offspring were fed HFD from weaning onward and analyzed at adulthood. The increases in body weight and leptin levels, but not glucose intolerance, induced by HFD were significantly augmented in the male, but not female, offspring from obese fathers. Paternal obesity caused a decrease in luteinizing hormone (LH) levels and exacerbated the drop in circulating testosterone and gene expression of its key biosynthetic enzymes caused by HFD in the male offspring. LH responses to central kisspeptin-10 administration were also suppressed in HFD males from obese fathers. In contrast, paternal obesity did not significantly alter gonadotropin levels in the female offspring fed HFD, although these females displayed reduced LH responses to kisspeptin-10. Our findings suggest that HFD-induced metabolic and reproductive disturbances are exacerbated by paternal obesity preferentially in males, whereas kisspeptin effects are affected in both sexes.
PB Oxford University Press
YR 201-
FD 201-7-12-19
LK http://hdl.handle.net/10668/11978
UL http://hdl.handle.net/10668/11978
LA en
NO Sanchez-Garrido MA, Ruiz-Pino F, Velasco I, Barroso A, Fernandois D, Heras V, et al. Intergenerational Influence of Paternal Obesity on Metabolic and Reproductive Health Parameters of the Offspring: Male-Preferential Impact and Involvement of Kiss1-Mediated Pathways. Endocrinology. 2018 Feb 1;159(2):1005-1018
NO This work was supported by Grants BFU2011-025021 and BFU2014-57581-P (Ministerio de Economía y Competitividad, Spain, cofunded with European Union funds from FEDER Program), Project PIE14-00005(Flexi-Met, Instituto de Salud Carlos III, Ministerio de Sanidad, Spain), Projects P08-CVI-03788 and P12-FQM-01943 (Junta de Andalucía, Spain), and European Union Research Contract DEER FP7-ENV-2007-1. CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of Instituto de Salud Carlos III.
DS RISalud
RD Apr 11, 2025