Sex differences in the expression of lipid oxidation and glucose uptake genes in muscles of fasted mice

Fasting has become increasingly popular for treatment and prevention of obesity. Sex differences in the mechanisms of adaptation to fasting may contribute to choosing a therapeutic strategy for correction of metabolic disorders. Hepatokine fibroblast growth factor 21 (FGF21) is involved in the adaptation to fasting. Muscles are assumed to be the main energy-consuming tissue in the body, as muscle metabolism plays an important role in the adaptation to nutritional deficit. However, there is still little information on sex differences in muscle and FGF21 physiological response to fasting. Our aim was to find out whether there were sex differences in hormonal regulation and the expression of genes controlling glucose and lipid metabolism in skeletal muscles in response to fasting. We estimated the effect of 24-hour fasting on the expression of genes involved in lipid (Ucp3, Cpt1) and carbohydrate (Slc2a4) metabolism in muscles and evaluated changes in body weight and blood plasma levels of glucose, insulin, free fatty acids (FFA), adiponectin, and FGF21 in male and female C57BL/6J mice. None of the genes studied (Ucp3, Cpt1 and Slc2a4) showed sex-related changes at mRNA levels in control groups, but females exposed to fasting demonstrated a significant increase in the expression of all genes as compared to control. Fasting significantly decreased body weight and glucose blood plasma levels in animals of both sexes but exerted no effect on the levels of insulin or FFA. The adiponectin and FGF21 levels were increased in response to fasting, the increase in females being significant. We were first to show sex dimorphism in muscle gene expression and FGF21 blood level in response to fasting. In females, the greater increase in FGF21 and adiponectin blood levels was positively associated with the greater upregulation of lipid oxidation and glucose uptake gene expression

Sex differences of molecular mechanisms of insulin sensitivity in young and adult C57BL/6J mice

Reduced insulin sensitivity plays an important role in the pathogenesis of type II diabetes. There are sex differences in the development of metabolic disorders. The aim of this work was to investigate the insulin signal transduction gene expression in mice of different sex and age. Male and female C57BL/6J mice were used in our studies. Gene expression was assayed by RT-PCR. It was shown that insulin sensitivity in females was higher than in males regardless of age because the level of glucose in blood plasma of females does not differ from that in males, whereas female insulin levels were lower than male insulin levels. Female glucose tolerance increased with age, and glucose tolerance was higher in females than in males at the age of 30 weeks. It was shown that sex and age affect the expressions of insulin signal transduction genes. It was shown that there are sex differences in the levels of mRNA Pik3cd in the liver, in the levels of mRNA Irs1 in the muscle, in the levels of mRNA Irs1 and Slc2a4 in adipose tissue at the age of 10 weeks, and there are sex differences in the levels of mRNA Irs2 and Pik3cd in the liver, in the levels mRNA Pik3cd and Slc2a4 in the muscle, in the levels mRNA Insr and Pik3cd in adipose tissue at the age of 30 weeks. In young animals, the expression of the genes was higher in females than in males in all tissues. In adult animals, the expression of the genes in the liver was higher in females than in males, the expression of the genes in muscle and adipose tissues were lower in females than in males. In males, the levels of mRNA Insr in the liver and muscles and mRNA Pik3cd in adipose tissue decreased with age, and the level of mRNA Pik3cd in muscles  increased with age. In females, the levels of mRNA Irs1 in muscle and mRNA Pik3cd and Slc2a4 in adipose tissue decreased with age. Thus the molecular basis of sex differences and age-related changes in insulin sensitivity may be a change in expressions of insulin signal transduction genes in the target tissues

Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation

The lethal yellow mutation in agouti loci (Ay mutation) reduces the activity of melanocortin (MC) receptors and causes hyperphagia, obesity and type two diabetes mellitus in aging mice (Ay mice). It is unknown if changes in distinct elements of the metabolic system such as white adipose tissue (WAT) and brown adipose tissue (BAT), and skeletal muscle will manifest before the development of obesity. The aim of this work was to measure the relative gene expression of key proteins that regulate carbohydrate-lipid metabolism in WAT, BAT and skeletal muscle in Ay mice before the development of obesity. C57Bl/6J mice bearing a dominant autosomal mutation Ay (Ay /a mice) and mice of the standard genotype (a/a mice, control) have been studied in three age groups: 10, 15 and 30 weeks. The relative mRNA level of genes was measured by real-time PCR in skeletal muscles (uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) (free fatty acids oxidation), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (glucose uptake)), in WAT lipoprotein lipase (Lpl) (triglyceride deposition), hormone-sensitive lipase (Lipe) (lipid mobilization), and Slc2a4 (glucose uptake)), and in BAT: uncoupling protein 1 (Ucp1) (energy expenditure). The expression of Cpt1b was reduced in young Ay mice (10 weeks), there was no transient peak of transcription of Cpt1b, Ucp3 in skeletal muscle tissue and Lipe, Slc2a4 in WAT in early adult Ay mice (15 weeks), which was noted in а/а mice. Reduction of the transcriptional activity of the studied genes in skeletal muscle and white adipose tissue can initiate the development of melanocortin obesity in Ay mice

Magnetoresistive study of antiferromagnetic--weak ferromagnetic transition in single-crystal La2_{2}CuO4+δ_{4+\delta}

The resistive measurements were made to study the magnetic field-induced antiferromagnetic (AF) - weak ferromagnetic (WF) transition in La$_2$CuO$_4$ single-crystal. The magnetic field (DC or pulsed) was applied normally to the CuO$_2$ layers. The transition manifested itself in a drastic decrease of the resistance in critical fields of ~5-7 T. The study is the first to display the effect of the AF -WF transition on the conductivity of the La$_2$CuO$_4$ single-crystal in the parallel - to - CuO$_2$ layers direction. The results provide support for the 3-dimensional nature of the hopping conduction of this layered oxide.Comment: 8 pages, 7 figures, RevTe

Estradiol-dependent and independent effects of FGF21 in obese female mice

The f ibroblast growth factor 21 (FGF21) synthesized in the liver, acting as a hormone, increases insulin sensitivity and energy expenditure. FGF21 administration has potent benef icial effects on obesity and diabetes in humans, cynomolgus monkey, and rodents. The therapeutic effects of FGF21 have been studied mainly in males. They are not always manifested in females, and they are accompanied by sex-specif ic activation of gene expression in tissues. We have suggested that one of the causes of sexual dimorphism in response to FGF21 is the effect of estradiol (E2). Currently, it is not known how estradiol modif ies the pharmacological effects of FGF21. The objective of this study was to study the inf luence of FGF21 on metabolic characteristics, food intake, and the expression of carbohydrate and fat metabolism genes in the liver, adipose tissue, and hypothalamus in female mice with alimentary obesity and low (ovariectomy) or high (ovariectomy + E2) blood estradiol level. In ovariectomized (OVX) females, the development of obesity was induced by the consumption of a high sweet-fat diet (standard chow, lard, and cookies) for 8 weeks. We investigated the effects of FGF21 on body weight, blood levels, food preferences and gene expression in tissues when FGF21 was administered separately or in combination with E2 for 13 days. In OVX obese females, FGF21, regardless of E2-treatment, did not affect body weight, and adipose tissue weight, or glucose tolerance but increased the consumption of standard chow, reduced blood glucose levels, and suppressed its own expression in the liver (Fgf21), as well as the expression of the G6pc and Acacα genes. This study is the f irst to show the modif ication of FGF21 effects by estradiol: inhibition of FGF21-inf luence on the expression of Irs2 and Pklr in the liver and potentiation of the FGF21-stimulated expression of Lepr and Klb in the hypothalamus. In addition, when administered together with estradiol, FGF21 exerted an inhibitory effect on the expression of Cpt1α in subcutaneous white adipose tissue (scWAT), whereas no stimulating FGF21 effects on the expression of Insr and Acacβ in scWAT or inhibitory FGF21 effect on the plasma insulin level were observed. The results suggest that the absence of FGF21 effects on body and adipose tissue weights in OVX obese females and its benef icial effect on food intake and blood glucose levels are not associated with the action of estradiol. However, estradiol affects the transcriptional effects of FGF21 in the liver, white adipose tissue, and hypothalamus, which may underlie sex differences in the FGF21 effect on the expression of metabolic genes and, possibly, in pharmacological FGF21 effects

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring

Obesity during pregnancy has been shown to increase the risk of metabolic diseases in the offspring. However, the factors within the maternal milieu which affect offspring phenotypes and the underlying mechanisms remain unknown. The adipocyte hormone leptin plays a key role in regulating energy homeostasis and is known to participate in sex‐specific developmental programming. To examine the action of leptin on fetal growth, placental gene expression and postnatal offspring metabolism, we injected C57BL mice with leptin or saline on gestational day 12 and then measured body weights (BWs) of offspring fed on a standard or obesogenic diet, as well as mRNA expression levels of insulin‐like growth factors and glucose and amino acid transporters. Male and female offspring born to leptin‐treated mothers exhibited growth retardation before and a growth surge after weaning. Mature male offspring, but not female offspring, exhibited increased BWs on a standard diet. Leptin administration prevented the development of hyperglycaemia in the obese offspring of both sexes. The placentas of the male and female foetuses differed in size and gene expression, and leptin injection decreased the fetal weights of both sexes, the placental weights of the male foetuses and placental gene expression of the GLUT1 glucose transporter in female foetuses. The data suggest that mid‐pregnancy is an ontogenetic window for the sex‐specific programming effects of leptin, and these effects may be exerted via fetal sex‐specific placental responses to leptin administration