Paternal obesity decreases infant MSC mitochondrial functional capacity.

Besides the well-recognized influence of maternal health on fetal in utero development, recent epidemiological studies appoint paternal pre-conception metabolic health as a significant factor in shaping fetal metabolic programming and subsequently offspring metabolic health; however, mechanisms behind these adaptations remain confined to animal models. To elucidate the effects of paternal obesity (P-OB) on infant metabolism in humans, we examined mesenchymal stem cells (MSCs) which give rise to infant tissue, remain involved in mature tissue maintenance, and resemble the phenotype of the offspring donor. Here, we assessed mitochondrial functional capacity, content, and insulin action in MSC from infants of fathers with overweight (BMI 25-30kg/m2) (P-OW) or obesity (BMI≥30kg/m2) (P-OB), while controlling for maternal intrauterine environment. Compared to P-OW, infant MSCs in the P-OB group had lower intact cell respiration, OXPHOS, and electron transport system capacity, independent of any changes in mitochondrial content. Furthermore, glucose handling, insulin action, and lipid content and oxidation were similar between groups. Importantly, infants in the P-OB group had a greater weight-to-length ratio, which could be in part due to changes in MSC metabolic functioning which precedes and therefore influences infant growth trajectories. These data suggest that P-OB negatively influences infant MSC mitochondria.

Exercise training and cold exposure trigger distinct molecular adaptations to inguinal white adipose tissue.

Exercise training and cold exposure both improve systemic metabolism, but the mechanisms are not well established. Here, we tested the hypothesis that inguinal white adipose tissue (iWAT) adaptations are critical for these beneficial effects and determined the impact of exercise-trained and cold-exposed iWAT on systemic glucose metabolism and the iWAT proteome and secretome. Transplanting trained iWAT into sedentary mice improves glucose tolerance, while cold-exposed iWAT transplantation shows no such benefit. Compared to training, cold leads to more pronounced alterations in the iWAT proteome and secretome, downregulating >2,000 proteins but also boosting the thermogenic capacity of iWAT. In contrast, only training increases extracellular space and vesicle transport proteins, and only training upregulates proteins that correlate with favorable fasting glucose, suggesting fundamental changes in trained iWAT that mediate tissue-to-tissue communication. This study defines the unique exercise training- and cold exposure-induced iWAT proteomes, revealing distinct mechanisms for the beneficial effects of these interventions on metabolic health.

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC).

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Chronic exercise improves hepatic acylcarnitine handling.

Exercise mediates tissue metabolic function through direct and indirect adaptations to acylcarnitine (AC) metabolism, but the exact mechanisms are unclear. We found that circulating medium-chain acylcarnitines (AC) (C12-C16) are lower in active/endurance trained human subjects compared to sedentary controls, and this is correlated with elevated cardiorespiratory fitness and reduced adiposity. In mice, exercise reduced serum AC and increased liver AC, and this was accompanied by a marked increase in expression of genes involved in hepatic AC metabolism and mitochondrial ß-oxidation. Primary hepatocytes from high-fat fed, exercise trained mice had increased basal respiration compared to hepatocytes from high-fat fed sedentary mice, which may be attributed to increased Ca2+ cycling and lipid uptake into mitochondria. The addition of specific medium- and long-chain AC to sedentary hepatocytes increased mitochondrial respiration, mirroring the exercise phenotype. These data indicate that AC redistribution is an exercise-induced mechanism to improve hepatic function and metabolism.

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue.

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

Diabetes, mitocondrias y ejercicio / Diabetes, mitochondria and exercise

El ejercicio produce efectos beneficiosos en la salud general de los individuos, y es indiscutible el papel que desempeña en el tratamiento y la prevención de la resistencia a la insulina y la diabetes tipo 2. Una sesión aguda de ejercicio o contracción muscular aumenta la captación de glucosa en el músculo esquelético a través de vías independientes de la insulina, y ello conduce a mejorías en la homeostasis corporal total de la glucosa. La actividad física regular induce cambios adaptativos en el músculo esquelético a través de modificaciones de la expresión de genes metabólicos. Estos cambios consisten en aumentos de las mitocondrias y modificaciones de la distribución de los tipos de fibras musculares. Un objetivo importante de la investigación sobre el ejercicio es el estudio de las señales moleculares que son inducidas por la actividad muscular y regulan los procesos metabólicos y transcripcionales clave en el músculo esquelético. En esta revisión, presentamos una breve panorámica general de la investigación sobre el ejercicio en el campo metabólico, describiendo diversas señales moleculares que subyacen en esos procesos. En este campo dinámico de investigación, se está realizando una búsqueda de otras proteínas de señalización estimuladas por el ejercicio. Los estudios que se realizan para aclarar en mayor medida las vías influidas por el ejercicio que intervienen en el transporte de glucosa, el tipo de fibra muscular y la biogénesis mitocondrial, permitirán comprender mejor cómo se producen los efectos favorables del ejercicio, mejorar nuestro conocimiento sobre los mecanismos patológicos de las enfermedades metabólicas como la diabetes tipo 2 e identificar nuevas dianas farmacológicas para el tratamiento (AU)

Exercise has beneficial effects on overall health, and its role in the treatment and prevention of insulin resistance and type 2 diabetes is undisputed. An acute bout of exercise or muscle contraction increases glucose uptake into skeletal muscle through insulin independent pathways, which leads to improvements in whole body glucose homeostasis. Regular physical activity induces adaptative changes in skeletal muscle through modification of metabolic gene expression. Such changes include increases in mitochondria and alteration of muscle fiber type distribution. An important goal of exercise research is to study molecular signals that are induced by muscle activity and that regulate key metabolic and transcriptional events in skeletal muscle. In this review, we give a brief overview of exercise research in the metabolic field, describing a number of molecular signals underlying these events. In this dynamic field of research the search for additional exercise-stimulated signalling proteins is ongoing. Studies to further elucidate exercise-mediated pathways involved in glucose transport, muscle fibre type and mitochondrial biogenesis will help to further understand the beneficial effects of exercise, to improve our knowledge about the pathological mechanisms of metabolic diseases such as type 2 diabetes, and to find new pharmacological targets for treatment (AU)