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Elevated leptin in pregnant mice improves metabolism in offspring fed high-calorie diet and its influence may be sex-specific. Molecular mechanisms mediating leptin programming action are unknown. We aimed to investigate programming actions of maternal leptin on the signaling function of the placenta and fetal liver and on adaptation to high-calorie diet in male and female offspring. Female C57BL/6J mice received leptin injections in mid-pregnancy. Gene expression was assessed in placentas and in the fetal brain and liver at the end of pregnancy. Metabolic parameters and gene expression in the liver, brown fat and hypothalamus were assessed in adult male and female offspring that had consumed sweet and fatty diet (SFD: chow, lard, sweet biscuits) for 2 weeks. Females had lower blood levels of leptin, glucose, triglycerides and cholesterol than males. Consuming SFD, females had increased Ucp1 expression in brown fat, while males had accumulated fat, decreased blood triglycerides and liver Fasn expression. Leptin administration to mothers increased Igf1 and Dnmt3b expression in fetal liver, decreased post-weaning growth rate, and increased hypothalamic Crh expression in response to SFD in both sexes. Only in male offspring this administration decreased expression of Fasn and Gck in the mature liver, increased fat mass, blood levels of glucose, triglycerides and cholesterol and Dmnt3a expression in the fetal liver. The results suggest that the influence of maternal leptin on the expression of genes encoding growth factors and DNA methyltransferases in the fetal liver may mediate its programming effect on offspring metabolic phenotypes.

The consumption of food rich in sugar and fat provokes obesity. Prenatal conditions have an impact on taste preferences and metabolism in the adult offspring, and this impact may manifest differently in different sexes. An increase in blood leptin level in pregnant females reduces the risk of obesity and insulin resistance in the offspring, although the mechanisms mediating this effect are unknown. Neither is it known whether maternal leptin affects taste preferences. In this study, we investigated the effect of leptin administration to pregnant mice on the development of diet-induced obesity, food choice, and gene expression in the liver and muscles of the offspring with regard to sex. Leptin was administered to female mice on days 11, 12, and 13 of pregnancy. In male and female offspring, growth rate and intake of standard chow after weaning, obesity development, gene expression in the liver and muscles, and food choice when kept on a high-calorie diet (standard chow, lard, sweet cookies) were recorded. Leptin administration to pregnant females reduced body weight in the female offspring fed on the standard diet. When the offspring were given a high-calorie diet, leptin administration inhibited obesity development and reduced the consumption of cookies only in males. It also increased the consumption of standard chow and the mRNA levels of genes for the insulin receptor and glucose transporter type 4 in the muscles of both male and female offspring. The results demonstrate that an increase in blood leptin levels in pregnant females has a sex-specific effect on the metabolism of the offspring increasing resistance to obesity only in male offspring. The mechanism underlying this effect includes a shift in food preference in favor of a balanced diet and maintenance of insulin sensitivity in muscle tissues.

Metabolic syndrome (MS) is a cluster of cardiometabolic factors that are strongly associated with the risk of serious chronic diseases. The prevalence of MS continues to grow, including among children, adolescents and people of active reproductive age. For the sphere of reproductive medicine, the problem of MS is of particular importance not only because of its negative impact on fertility, the frequency of complications of pregnancy and childbirth, but also because of its transgenerative effect on the health of offspring: it is proved that each of the components of the metabolic syndrome is a powerful epigenetic factor. Recent studies have revealed many new facets of the pathogenesis of MS and expanded the range of its etiologic factors beyond the alimentary factors, which determines the possibility of finding new approaches to prevention and treatment of this pathology. The review presents: evolution of diagnostic criteria for MS and reflection of this process in epidemiology and clinical approaches to the disease; epidemiological data on the prevalence of MS in young adults. A brief overview of a large array of scientific research of the last decade on etiology and pathogenesis of MS, in particular the role of adipose tissue dysfunction of visceral, ileofemoral and ectopic depots, causes of the tendency to prevail in one or another adipose tissue depot, new obesity classification, as well as the role of perinatal and epigenetic, ecological (environmental obesogenes, artificial light contamination), composition of intestinal microbiota, state of the sympathetic nervous system, nutritional deficiencies in the development of obesity and MS is provided. The gender differences of pathogenesis and clinical features of MS, as well as the association of MS with dyshormonal and other pathologies (PCOS, hyperprolactinemia, uterine myoma, endometriosis) of female reproductive health are considered.