Combined parental obesity augments single-parent obesity effects on hypothalamus inflammation, leptin signaling (JAK/STAT), hyperphagia, and obesity in the adult mice offspring.
We aimed to evaluate the effects of maternal and/or paternal obesity on offspring body mass, leptin signaling, appetite-regulating neurotransmitters and local inflammatory markers. C57BL/6 mice received standard chow (SC, lean groups) or high-fat diet (HF, obese groups) starting from one month of age. At three months, HF mice became obese relative to SC mice. They were then mated as follows: lean mother and lean father, lean mother and obese father, obese mother and lean father, and obese mother and obese father. The offspring received the SC diet from weaning until three months of age, when they were sacrificed. In the offspring, paternal obesity did not lead to changes in the Janus kinase (JAK)/signal transducer and activation of the transcription (STAT) pathway or feeding behavior but did induce hypothalamic inflammation. On the other hand, maternal obesity resulted in increased weight gain, hyperleptinemia, decreased leptin OBRb receptor expression, JAK/STAT pathway impairment, and increased SOCS3 signaling in the offspring. In addition, maternal obesity elevated inflammatory markers and altered NPY and POMC expression in the hypothalamus. Interestingly, combined parental obesity exacerbated the deleterious outcomes compared to single-parent obesity. In conclusion, while maternal obesity is known to program metabolic changes and obesity in offspring, the current study demonstrated that obese fathers induce hypothalamus inflammation in offspring, which may contribute to the development of metabolic syndromes in adulthood.
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: cruz.fop@gmail.com.
Fernanda
F
Ornellas
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: souzamello.uerj@gmail.com.
Vanessa
V
Souza-Mello
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mandarim@uerj.br.
Carlos Alberto
CA
Mandarim-de-Lacerda
Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: marciaguila@gmail.com.
Marcia Barbosa
MB
Aguila
D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat; D002149:Energy Intake; D005220:Fathers; D005260:Female; D006963:Hyperphagia / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D009035:Mothers; D009478:Neuropeptide Y / Q000096:biosynthesis; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010290:Parents; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D054411:Receptors, Leptin / Q000096:biosynthesis; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
D018836:Inflammation Mediators; D020738:Leptin; D009478:Neuropeptide Y; D054411:Receptors, Leptin; D050794:STAT1 Transcription Factor; C491411:Socs3 protein, mouse; C494080:Stat1 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D011333:Pro-Opiomelanocortin; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1
Eating behavior; Hypothalamus; Mice; Obese father; Obese mother; Parental obesity