Strength Training Protects High-Fat-Fed Ovariectomized Mice against Insulin Resistance and Hepatic Steatosis.

Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle changes, including a balanced diet and physical exercise, are necessary to prevent these undesirable changes. Strength training (ST) has been widely used because of the muscle and metabolic benefits it provides. Our study aims to evaluate the effects of ST on hepatic steatosis and insulin resistance in ovariectomized mice fed a high-fat diet (HFD) divided into four groups as follows: simulated sedentary surgery (SHAM-SED), trained simulated surgery (SHAM-EXE), sedentary ovariectomy (OVX-SED), and trained ovariectomy (OVX-EXE). They were fed an HFD for 9 weeks. ST was performed thrice a week. ST efficiently reduced body weight and fat percentage and increased lean mass in OVX mice. Furthermore, ST reduced the accumulation of ectopic hepatic lipids, increased AMPK phosphorylation, and inhibited the de novo lipogenesis pathway. OVX-EXE mice also showed a better glycemic profile, associated with greater insulin sensitivity identified by the euglycemic-hyperinsulinemic clamp, and reduced markers of hepatic oxidative stress compared with sedentary animals. Our data support the idea that ST can be indicated as a non-pharmacological treatment approach to mitigate metabolic changes resulting from menopause.

Progesterone Has No Impact on the Beneficial Effects of Estradiol Treatment in High-Fat-Fed Ovariectomized Mice.

In recent decades, clinical and experimental studies have revealed that estradiol contributes enormously to glycemic homeostasis. However, the same consensus does not exist in women during menopause who undergo replacement with progesterone or conjugated estradiol and progesterone. Since most hormone replacement treatments in menopausal women are performed with estradiol (E2) and progesterone (P4) combined, this work aimed to investigate the effects of progesterone on energy metabolism and insulin resistance in an experimental model of menopause (ovariectomized female mice-OVX mice) fed a high-fat diet (HFD). OVX mice were treated with E2 or P4 (or both combined). OVX mice treated with E2 alone or combined with P4 displayed reduced body weight after six weeks of HFD feeding compared to OVX mice and OVX mice treated with P4 alone. These data were associated with improved glucose tolerance and insulin sensitivity in OVX mice treated with E2 (alone or combined with P4) compared to OVX and P4-treated mice. Additionally, E2 treatment (alone or combined with P4) reduced both hepatic and muscle triglyceride content compared with OVX control mice and OVX + P4 mice. There were no differences between groups regarding hepatic enzymes in plasma and inflammatory markers. Therefore, our results revealed that progesterone replacement alone does not seem to influence glucose homeostasis and ectopic lipid accumulation in OVX mice. These results will help expand knowledge about hormone replacement in postmenopausal women associated with metabolic syndrome and non-alcoholic fatty liver disease.

Intrauterine malnutrition disrupts leptin and ghrelin milk hormones, programming rats.

Herein, we assessed milk hormones, the biochemical composition of milk, and its association with neonatal body weight gain and metabolic homeostasis in weaned rats whose mothers were undernourished in the last third of pregnancy. From the 14th day of pregnancy until delivery, undernourished mothers had their food restricted by 50% (FR50), whereas control mothers were fed ad libitum. The litter size was adjusted to eight pups, and rats were weaned at 22 days old. Milk and blood from mothers, as well as blood and tissues from pups, were collected for further analyses. At birth, FR50 pups were smaller than control pups, and they exhibited hyperphagia and rapid catch-up growth during the suckling period. On day 12, the milk from FR50 mothers had higher energy content, glucose, total cholesterol, triglycerides, and acylated ghrelin but lower leptin and corticosterone levels. Interestingly, FR50 mothers were hypoglycemic and hyperleptinemic at the end of the nursing period. Weaned FR50 pups had an obese phenotype and exhibited insulin resistance, which was associated with hyperglycemia and hypertriglyceridemia; they also had high blood levels of total cholesterol, leptin, and acylated ghrelin. In addition, the protein expression of growth hormone secretagogue receptor (GHSR) in the hypothalamus was increased by almost 4-fold in FR50 pups. In summary, maternal calorie restriction during the last third of pregnancy disrupts energy and metabolic hormones in milk, induces pup hyperleptinemia and hyperghrelinemia, and upregulates their hypothalamic GHSR, thus suggesting that the hypothalamic neuroendocrine circuitry may be working to address the early onset of obesity.

Epinephrine increases contextual learning through activation of peripheral ß2-adrenoceptors.

RATIONALE: Phenylethanolamine-N-methyltransferase knockout (Pnmt-KO) mice are unable to synthesize epinephrine and display reduced contextual fear. However, the precise mechanism responsible for impaired contextual fear learning in these mice is unknown. OBJECTIVES: Our aim was to study the mechanism of epinephrine-dependent contextual learning. METHODS: Wild-type (WT) or Pnmt-KO (129x1/SvJ) mice were submitted to a fear conditioning test either in the absence or in the presence of epinephrine, isoprenaline (non-selective ß-adrenoceptor agonist), fenoterol (selective ß2-adrenoceptor agonist), epinephrine plus sotalol (non-selective ß-adrenoceptor antagonist), and dobutamine (selective ß1-adrenoceptor agonist). Catecholamines were separated by reverse-phase HPLC and quantified by electrochemical detection. Blood glucose was measured by coulometry. RESULTS: Re-exposure to shock context induced higher freezing in WT and Pnmt-KO mice treated with epinephrine and fenoterol than in mice treated with vehicle. In addition, freezing response in Pnmt-KO mice was much lower than in WT mice. Freezing induced by epinephrine was blocked by sotalol in Pnmt-KO mice. Epinephrine and fenoterol treatment restored glycemic response in Pnmt-KO mice. Re-exposure to shock context did not induce a significant difference in freezing in Pnmt-KO mice treated with dobutamine and vehicle. CONCLUSIONS: Aversive memories are best retained if moderately high plasma epinephrine concentrations occur at the same moment as the aversive stimulus. In addition, epinephrine increases context fear learning by acting on peripheral ß2-adrenoceptors, which may induce high levels of blood glucose. Since glucose crosses the blood-brain barrier, it may enhance hippocampal-dependent contextual learning.