Abstract
In rodents, the most adequate model of human diet-induced obesity is obesity caused by the consumption of a sweet-fat diet (SFD), which causes more pronounced adiposity in females than in males. The aim of this work was to determine the sex-associated effect of SFD on the expression of genes related to carbohydrate-lipid metabolism in adult mice. For 10 weeks, male and female С57Bl mice were fed a standard laboratory chow (Control group) or a diet, which consisted of laboratory chow supplemented with sweet cookies, sunflower seeds and lard (SFD group). Weights of body, liver and fat depots, blood concentrations of hormones and metabolites, liver fat, and mRNA levels of genes involved in regulation of energy metabolism in the liver, perigonadal and subcutaneous white adipose tissue (pgWAT, scWAT) and brown adipose tissue (BAT) were measured. SFD increased body weight and insulin resistance in mice of both sexes. Female mice that consumed SFD (SFD females) had a greater increase in adiposity than SFD males. SFD females showed a decreased expression of genes related to lipogenesis (Lpl) and glucose metabolism (G6pc, Pklr) in liver, as well as lipogenesis (Lpl, Slca4) and lipolysis (Lipe) in pgWAT, suggesting reduced energy expenditure. In contrast, SFD males showed increased lean mass gain, plasma insulin and FGF21 levels, expressions of Cpt1α gene in pgWAT and scWAT and Pklr gene in liver, suggesting enhanced lipid and glucose oxidation in these organs. Thus, in mice, there are sex-dependent differences in adaptation to SFD at the transcriptional level, which can help to explain higher adiposity in females under SFD consumtion.
Highlights
In the human population, there is a significant increase in the number of people suffering from obesity and associated metabolic diseases such as type 2 diabetes, cardiovascular diseases and non-alcoholic fatty liver
Ten-week-old C57BL mice were used. Both male and female mice were housed in group (3 mice per cage) and were fed with standard laboratory chow (Assortiment Agro, Moscow region, Turacovo, Russia) or with mixed diet, which consisted of standard laboratory chow supplemented with sweet cookies, sunflower seeds and lard
Our results showed that the sweet-fat diet (SFD) consumption stimulated the development of metabolic syndrome regardless of sex: obesity, increased blood glucose, insulin, cholesterol levels, hepatic TG content, and decreased glucose tolerance and insulin sensitivity
Summary
There is a significant increase in the number of people suffering from obesity and associated metabolic diseases such as type 2 diabetes, cardiovascular diseases and non-alcoholic fatty liver. The mechanisms of obesity development are studied in laboratory animals with various models of diet-induced obesity. SFD is most consistent with the consumption of “pleasant” food, which provokes the development of obesity in the human population (Sampey et al, 2011). A special study carried out on male rats showed that SFD more effectively than a high-fat diet induced the development of obesity, hyperphagia, and increased blood cholesterol and leptin levels (Buyukdere et al, 2019). The question of the impact of sex on the adaptation of adult mice to long-term consumption of a SFD remains unexplored
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