P-023 Weight loss in obese fathers improves hepatic lipid metabolism in offspring

Abstract

Abstract Study question Does paternal obesity affect offspring lipid metabolism and whether paternal weight loss can correct this effect? Summary answer The lipid metabolism of male offspring of obese fathers is abnormal, especially under the second hit, and paternal weight loss could rescue it. What is known already So far we have known that epigenetic modifications in spermatogenesis, are directly involved in the etiopathology of adult diseases transmitted by sperm. It was found that the offspring had more weight gain and impaired glucose tolerance and insulin resistance in adulthood, although they kept a normal diet through microinjecting ncRNA of obese mice spermatozoa into fertilized eggs from normal parents. The above evidence supported that epigenetic modifications can undertake part of the transmission from father to offspring. Study design, size, duration The 30 4-week-old C57 male mice were divided into three groups, normal diet as the control group (NCD) for 30 weeks, high-fat diet as the obese group (HFD) for 30 weeks, first high-fat diet for 10 weeks then low-fat and high-fiber diet as weight loss for 20 weeks (LFD). The male offspring of these groups were normally fed after weaning, then received a second hit (fasting for 36 hours or high-fat diet for 4 weeks). Participants/materials, setting, methods These offspring were divided NCD F1, HFD F1 and LFD F1, respectively. And in the fasting condition, the oil tolerance test and P407 test were carried out to detect the hepatic lipid metabolism function. HE staining and Oil Red O staining were performed on the liver sections of offspring to clarify the accumulation of lipid droplets in the liver. Liver autophagy was detected by western blotting and confocal microscopy. Main results and the role of chance Through oil tolerance test, it was found that TG and NEFA of HFD F1 increased at 1 hour and 3 hours after gavage, while LFD F1 significantly decreased. The P407 test further proved that under fasting conditions, the release of TG from the liver of HFD F1 was significantly weakened, and LFD F1 was restored. HE staining and Oil Red O staining of liver sections indicated that lipid droplets accumulated in the liver of HFD F1, while LFD F1 were significantly reduced. Under the second hit, the difference in liver lipid droplets among the three groups was more obvious. In addition, we found the levels of serum C-reactive protein, TNFα, and IL-6 increased in HFD F1 under the second hit, while LFD F1 could restore. It was found that the p62 of HFD F1 was higher and the ratio of LC3II to LC3I was lower than that of NCD F1, which indicated that HFD offspring liver autophagy was weakened through western blotting, and LFD offspring could restore liver autophagy. It was found that the co-localization of lipid droplets and lysosomes in the HFD offspring was reduced, which was more obvious under the second hit, while the LFD offspring could recover. Limitations, reasons for caution This study provides phenotypic evidence, however, the genetics of paternal disease remain to be explored. Wider implications of the findings The study provides new evidence that the father's lifestyle affects offspring metabolism, but this effect is not permanent and can be eliminated by changing the lifestyle. Trial registration number 82088102