Fas (CD95) expression in adipocytes contributes to diet-induced obesity.

Objective: Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.

Methods: Adipocyte-specific Fas knockout (Fas) and control littermate (Fas) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks.

Impaired Mitochondrial Respiration in Upper Compared to Lower Body Differentiated Human Adipocytes and Adipose Tissue.

Context: Abdominal obesity is associated with increased cardiometabolic disease risk, while lower body fat seems to confer protection against obesity-related complications. The functional differences between upper and lower body adipose tissue (AT) remain poorly understood.

Objective: We aimed to examine whether mitochondrial respiration is impaired in abdominal as compared to femoral differentiated human multipotent adipose-derived stem cells (hMADS; primary outcome) and AT in postmenopausal women.

Distinct inflammatory signatures of upper and lower body adipose tissue and adipocytes in women with normal weight or obesity.

Introduction: Upper and lower body fat accumulation poses an opposing obesity-related cardiometabolic disease risk. Depot-differences in subcutaneous adipose tissue (SAT) function may underlie these associations. We aimed to investigate the inflammatory signatures of abdominal (ABD) and femoral (FEM) SAT in postmenopausal women with normal weight or obesity.

Emotional and psychosexual well-being is influenced by ethnicity and birthplace in women and individuals with polycystic ovary syndrome in the UK and India.

Objective: To assess the association of ethnicity and birthplace on emotional and psychosexual well-being in women with polycystic ovary syndrome (PCOS).

Design: Cross-sectional study.

Setting: Community recruitment via social media campaigns.

Physiological Oxygen Levels Differentially Regulate Adipokine Production in Abdominal and Femoral Adipocytes from Individuals with Obesity Versus Normal Weight.

Adipose tissue (AT) inflammation may increase obesity-related cardiometabolic complications. Altered AT oxygen partial pressure (pO) may impact the adipocyte inflammatory phenotype. Here, we investigated the effects of pO levels on the inflammatory phenotype of abdominal (ABD) and femoral (FEM) adipocytes derived from postmenopausal women with normal weight (NW) or obesity (OB).

The effect of intranasal insulin on appetite and mood in women with and without obesity: an experimental medicine study.

Background/objectives: Intranasal (IN) administration of insulin decreases appetite in humans, but the underlying mechanisms are unclear, and it is unknown whether IN insulin affects the food intake of women with obesity.

Subjects/methods: In a double-blind, placebo-controlled, crossover design, participants (35 lean women and 17 women with obesity) were randomized to receive 160 IU/1.6 mL of IN insulin or placebo in a counterbalanced order in the post prandial state.

Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.

Background: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined.

Objective: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS.

Thyroid hormone alterations in critically and non-critically ill patients with SARS-CoV-2 infection.

Objective: Following the evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis-related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, we studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients.

Measurement of human abdominal and femoral intravascular adipose tissue blood flow using percutaneous Doppler ultrasound.

Adipose tissue blood flow (ATBF) is an important determinant of adipose tissue (AT) function. Xenon wash-out technique is considered the gold-standard for human ATBF measurements. However, decreasing Xenon clinical use and costly production and preservation, make alternative (non-invasive) methods necessary.

The effect of short-term exercise prehabilitation on skeletal muscle protein synthesis and atrophy during bed rest in older men.

Background: Poor recovery from periods of disuse accelerates age-related muscle loss, predisposing individuals to the development of secondary adverse health outcomes. Exercise prior to disuse (prehabilitation) may prevent muscle deterioration during subsequent unloading. The present study aimed to investigate the effect of short-term resistance exercise training (RET) prehabilitation on muscle morphology and regulatory mechanisms during 5 days of bed rest in older men.

Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) has been traditionally perceived as a reproductive disorder due to its most common presentation with menstrual dysfunction and infertility. However, it is now clear that women with PCOS are at increased risk of metabolic dysfunction, from impaired glucose tolerance and type 2 diabetes mellitus to nonalcoholic fatty liver disease and cardiovascular disease. PCOS is characterised by androgen excess, with cross-sectional data showing that hyperandrogenism is directly complicit in the development of metabolic complications.

Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese.

Context: Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness.

Objective: To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism.

Design: (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study).

Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.

Nicotinamide adenine dinucleotide (NAD) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD metabolome and if it can alter muscle mitochondrial bioenergetics.

Oxygenation of adipose tissue: A human perspective.

Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low-grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results.

Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort.

Objective: Previous studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex-specific link between circulating androgens and risk of type 2 diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study.

Design: A retrospective cohort study in a UK primary care database.

Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database.

Background: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver.

Methods And Findings: We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016.

AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome.

Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking.

Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo.

Introduction: Brown adipose tissue (BAT) is a thermogenic organ with substantial metabolic capacity and has important roles in the maintenance of body weight and metabolism. Regulation of BAT is primarily mediated through the β-adrenoceptor (β-AR) pathway. The in vivo endocrine regulation of this pathway in humans is unknown.

Acute Hypercortisolemia Exerts Depot-Specific Effects on Abdominal and Femoral Adipose Tissue Function.

Context: Glucocorticoids have pleiotropic metabolic functions, and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear.

Objective: To provide an in vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration.

Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications.

Upper- and lower-body fat depots exhibit opposing associations with obesity-related metabolic disease. We defined the relationship between DEXA-quantified fat depots and diabetes/cardiovascular risk factors in a healthy population-based cohort (n = 3,399). Gynoid fat mass correlated negatively with insulin resistance after total fat mass adjustment, whereas the opposite was seen for abdominal fat.

Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake.

Glucocorticoids increase adipocyte proliferation and differentiation, a process underpinned by the local reactivation of inactive cortisone to active cortisol within adipocytes catalyzed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal sex steroid precursor dehydroepiandrosterone (DHEA) has been shown to inhibit 11β-HSD1 in murine adipocytes; however, rodent adrenals do not produce DHEA physiologically. Here, we aimed to determine the effects and underlying mechanisms of the potential antiglucocorticoid action of DHEA and its sulfate ester DHEAS in human preadipocytes.

Recycling between cortisol and cortisone in human splanchnic, subcutaneous adipose, and skeletal muscle tissues in vivo.

11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) is a therapeutic target in metabolic syndrome because it catalyses reductase regeneration of cortisol from cortisone in adipose and liver. 11βHSD1 can also catalyze the reverse dehydrogenase reaction in vitro (e.g.