European Journal of Nutrition

, Volume 57, Issue 5, pp 1901–1912 | Cite as

Father’s obesity programs the adipose tissue in the offspring via the local renin–angiotensin system and MAPKs pathways, especially in adult male mice

  • Fernanda Ornellas
  • Isabele Bringhenti
  • Brenda Akemi N. F. Mattos
  • Carlos Alberto Mandarim-de-Lacerda
  • Marcia Barbosa Aguila
Original Contribution



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.


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.


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).


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.


Adipocyte Genital fat pad Programming Inflammation Molecular biology 



AMP-activated protein kinase


Ang-II type 1 receptor


Angiotensin-converting enzyme




c-Jun N-terminal kinase


Extracellular signal-regulated kinase 1/2


Factor nuclear kappa B


Insulin receptor substrate 1




Mitogen-activated protein kinases


Peroxisome proliferator-activated receptor


Protein kinase B


Renin–angiotensin system


TATA box-binding protein


Tumor necrosis factor-alpha


White adipose tissue



The authors would like to thank Michele Soares and Aline Penna de Carvalho for technical assistance.

Author’s contribution

Conception/design of the work: FO, MBA; Data collection: FO.

IB, BM; Data analysis and interpretation: FO, IB, CAML, MBA; Drafting the article: FO, IB.

MBA; Critical revision of the article: CAML, MBA; Final approval of the version to be published: CAML, MBA.

Compliance with ethical standards

Experimental protocol was approved by the Ethics Committee of the State University of Rio de Janeiro (Protocol Number CEUA 070/2012).

Conflict of interest

The authors disclose no conflict of interest in the study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Universidade do Estado do Rio de Janeiro, Centro Biomédico, Instituto de Biologia, Laboratório de Morfometria, Metabolismo e Doença CardiovascularRio de JaneiroBrazil

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