Increasing caloric intake is a promising treatment for exercise-associated amenorrhea, but strategies have not been fully explored. The purpose of this case report was to compare and contrast the responses of two exercising women with amenorrhea of varying duration to an intervention of increased energy intake. Two exercising women with amenorrhea of short (3 months) and long (11 months) duration were chosen to demonstrate the impact of increased caloric intake on recovery of menstrual function and bone health. Repeated measures of dietary intake, eating behavior, body weight, body composition, bone mineral density, resting energy expenditure, exercise volume, serum metabolic hormones and markers of bone turnover, and daily urinary metabolites were obtained. Participant 1 was 19 years old and had a body mass index (BMI) of 20.4 kg/m 2 at baseline. She increased caloric intake by 276 kcal/day (1,155 kJ/day, 13%), on average, during the intervention, and her body mass increased by 4.2 kg (8%). Participant 2 was 24 years old and had a BMI of 19.7 kg/m 2 . She increased caloric intake by 1,881 kcal/ day (7,870 kJ/day, 27%) and increased body mass by 2.8 kg (5%). Resting energy expenditure, triiodothyronine, and leptin increased; whereas, ghrelin decreased in both women. Resumption of menses occurred 23 and 74 days into the intervention for the women with short-term and long-term amenorrhea, respectively. The onset of ovulation and regular cycles corresponded with changes in body weight. Recovery of menses coincided closely with increases in caloric intake, weight gain, and improvements in the metabolic environment; however, the nature of restoration of menstrual function differed between the women with short-term versus long-term amenorrhea.

Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes.

Intrauterine growth restriction (IUGR) programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNFα). TNFα contributes to adipocyte inflammation and impaired insulin signaling. TNFα has also been implicated in the activation of the unfolded protein response (UPR), which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNFα, TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2α, and Ddit3) prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1) increased circulating and adipose TNFα, (2) increased mRNA levels of UPR components as well as p-eIF2a, and (3) impaired glucose tolerance after observed TNFα increased and after UPR activation. We speculate that programmed dysregulation of TNFα and UPR contributed to the development of glucose intolerance in male IUGR rats.

Activation of satellite cells and expansion of the muscle progenitor cell (MPC) population is essential to generate a sufficient number of cells to repair damaged skeletal muscle. Proliferating MPCs have high energetic and biosynthetic material requirements, and the ability to utilize oxidative phosphorylation (OXPHOS) and/or glycolysis may affect expansion capacity of MPCs. In the present study, we investigated whether donor age and sex impact human MPC (hMPCs) expansion capacity and metabolic fuel preference. hMPCs from young and old males and females were grown for 408 h (17 days). Percent confluency, live nuclei count, and dead cell count were measured every 24 h. Metabolic phenotype was assessed using glucose uptake, expression of genes related to glycolysis and OXPHOS, and the Seahorse XF24 Phenotype Test Kit during the exponential phase of growth. hMPCs from old male donors had impaired expansion capacity secondary to heightened cell death early in expansion compared to hMPCs from young male donors, an effect not observed in female hMPCs. Age-related differences in metabolism were also sex-dependent; markers of OXPHOS were altered in old (vs. young) male hMPCs while markers of metabolism were largely unaffected by age in female hMPCs. For the first time, we identify sex-specific differences in cell death and OXPHOS that contribute to altered expansion capacity of hMPC cell populations with age.

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