Neuropeptide Y Overexpressing Female and Male Mice Show Divergent Metabolic but Not Gut Microbial Responses to Prenatal Metformin Exposure

• Published in: PloS one Vol. 11; no. 9; p. e0163805
• Main Authors: Salomäki-Myftari, Henriikka, Vähätalo, Laura H, Ailanen, Liisa, Pietilä, Sami, Laiho, Asta, Hänninen, Arno, Pursiheimo, Juha-Pekka, Munukka, Eveliina, Rintala, Anniina, Savontaus, Eriika, Pesonen, Ullamari, Koulu, Markku
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-09-2016; Public Library of Science (PLoS)
• Subjects: Analysis; Antibiotics; Antidiabetics; Bioinformatics; Biology and Life Sciences; Body composition; Body composition (biology); Body fat; Body weight; Body weight gain; Brain; Brain research; Cholesterol; Diabetes; Diabetic retinopathy; Diet; Exposure; Gastroenterology; Gene expression; Glucose; Glucose tolerance; High fat diet; Hyperglycemia; Immunology; Insulin; Intestinal microflora; Lipids; Medicine and Health Sciences; Metabolism; Metformin; Mice; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Neuropeptide Y; Neuropeptides; Norepinephrine; Obesity; Offspring; Pharmacology; Phenotypes; Physiological aspects; Pregnant women; Prenatal experience; RNA; Rodents; rRNA 16S; Sutterella; Sympathetic nervous system; Systematic review; Type 2 diabetes; Weaning; Finland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163805

Prenatal metformin exposure has been shown to improve the metabolic outcome in the offspring of high fat diet fed dams. However, if this is evident also in a genetic model of obesity and whether gut microbiota has a role, is not known.
The metabolic effects of prenatal metformin exposure were investigated in a genetic model of obesity, mice overexpressing neuropeptide Y in the sympathetic nervous system and in brain noradrenergic neurons (OE-NPYDβH). Metformin was given for 18 days to the mated female mice. Body weight, body composition, glucose tolerance and serum parameters of the offspring were investigated on regular diet from weaning and sequentially on western diet (at the age of 5-7 months). Gut microbiota composition was analysed by 16S rRNA sequencing at 10-11 weeks.
In the male offspring, metformin exposure inhibited weight gain. Moreover, weight of white fat depots and serum insulin and lipids tended to be lower at 7 months. In contrast, in the female offspring, metformin exposure impaired glucose tolerance at 3 months, and subsequently increased body weight gain, fat mass and serum cholesterol. In the gut microbiota, a decline in Erysipelotrichaceae and Odoribacter was detected in the metformin exposed offspring. Furthermore, the abundance of Sutterella tended to be decreased and Parabacteroides increased. Gut microbiota composition of the metformin exposed male offspring correlated to their metabolic phenotype.
Prenatal metformin exposure caused divergent metabolic phenotypes in the female and male offspring. Nevertheless, gut microbiota of metformin exposed offspring was similarly modified in both genders.