17α-Estradiol alleviates high-fat diet-induced inflammatory and metabolic dysfunction in skeletal muscle of male and female mice.

17α-estradiol (17α-E2) is a naturally occurring nonfeminizing diastereomer of 17ß-estradiol that has life span-extending effects in rodent models. To date, studies of the systemic and tissue-specific benefits of 17α-E2 have largely focused on the liver, brain, and white adipose tissue with far less focus on skeletal muscle. Skeletal muscle has an important role in metabolic and age-related disease. Therefore, this study aimed to determine whether 17α-E2 treatment has positive, tissue-specific effects on skeletal muscle during a high-fat feeding. We hypothesized that male, but not female, mice, would benefit from 17α-E2 treatment during a high-fat diet (HFD) with changes in the mitochondrial proteome to support lipid oxidation and subsequent reductions in diacylglycerol (DAG) and ceramide content. To test this hypothesis, we used a multiomics approach to determine changes in lipotoxic lipid intermediates, metabolites, and proteins related to metabolic homeostasis. Unexpectedly, we found that 17α-E2 had marked, but different, beneficial effects within each sex. In male mice, we show that 17α-E2 alleviates HFD-induced metabolic detriments of skeletal muscle by reducing the accumulation of diacylglycerol (DAG), and inflammatory cytokine levels, and altered the abundance of most of the proteins related to lipolysis and ß-oxidation. Similar to male mice, 17α-E2 treatment reduced fat mass while protecting muscle mass in female mice but had little muscle inflammatory cytokine levels. Although female mice were resistant to HFD-induced changes in DAGs, 17α-E2 treatment induced the upregulation of six DAG species. In female mice, 17α-E2 treatment changed the relative abundance of proteins involved in lipolysis, ß-oxidation, as well as structural and contractile proteins but to a smaller extent than male mice. These data demonstrate the metabolic benefits of 17α-E2 in skeletal muscle of male and female mice and contribute to the growing literature of the use of 17α-E2 for multi tissue health span benefits.NEW & NOTEWORTHY Using a multiomics approach, we show that 17α-E2 alleviates HFD-induced metabolic detriments in skeletal muscle by altering bioactive lipid intermediates, inflammatory cytokines, and the abundance of proteins related to lipolysis and muscle contraction. The positive effects of 17α-E2 in skeletal muscle occur in both sexes but differ in their outcome.

Structural equation modelling provides insights to understand the construct of chronic pain in women with rheumatoid arthritis.

OBJECTIVES: We aimed to adopt a multidimensional approach and investigate the interconnections between biomarkers (cytokines, matrix metalloproteinases, and cortisol) and psychosocial aspects considering pain acceptance, the individual construct of pain perception in terms of blood inflammation biomarkers, anxiety, self-efficacy, and functional performance and to define the quality of life (QoL) in women with rheumatoid arthritis (RA). METHODS: An observational cross-sectional study with a total of 42-RA participants, with chronic pain and 42-women without rheumatic diseases or chronic pain were included. A structural equation model was used to investigate the association between independent variables. RESULTS: Women with RA presented high blood biomarker levels, representing an intense inflammatory process. The participants with RA reported moderate pain most of the time, a worsening QoL, functionality, engagement in activities, and a willingness to live with pain and self-efficacy. It was found that the higher the chronic pain, the greater the intensity of pain perceived by these women with RA, as well as, the worse the functionality, the higher the perceived pain. CONCLUSIONS: The exacerbation of pain perception leads to worsening of the experience of chronic pain. The new construct of pain experience should include functionality as a crucial factor in understanding the mechanisms underlying pain.

Impact of paternal exercise on physiological systems in the offspring.

A significant number of studies have demonstrated that paternal exercise modulates future generations via effects on the sperm epigenome. However, comprehensive information regarding the effects of exercise performed by the father on different tissues and their clinical relevance has not yet been explored in detail. This narrative review is focused on the effects of paternal exercise training on various physiological systems of offspring. A detailed mechanistic understanding of these effects could provide crucial clues for the exercise physiology field and aid the development of therapeutic approaches to mitigate disorders in future generations. Non-coding RNA and DNA methylation are major routes for transmitting epigenetic information from parents to offspring. Resistance and treadmill exercise are the most frequently used modalities of planned and structured exercise in controlled experiments. Paternal exercise orchestrated protective effects over changes in fetus development and placenta inflammatory status. Moreover paternal exercise promoted modifications in the ncRNA profiles, gene and protein expression in the hippocampus, left ventricle, skeletal muscle, tendon, liver and pancreas in the offspring, while the transgenerational effects are unknown. Paternal exercise demonstrates clinical benefits to the offspring and provides a warning on the harmful effects of a paternal unhealthy lifestyle. Exercise in fathers is presented as one of the most logical and cost-effective ways of restoring health in the offspring and, consequently, modifying the phenotype. It is important to consider that paternal programming might have unique significance in the developmental origins of offspring diseases.