Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.

Estimating effects of longitudinal and cumulative exposure to PFAS mixtures on early adolescent body composition.

Few methods have been used to characterize repeatedly measured biomarkers of chemical mixtures. We applied latent profile analysis (LPA) to serum concentrations of 4 perfluoroalkyl and polyfluoroalkyl substances (PFAS) measured at 4 time points from gestation to age 12 years. We evaluated the relationships between profiles and z scores of height, body mass index, fat mass index, and lean body mass index at age 12 years (n = 218). We compared LPA findings with an alternative approach for cumulative PFAS mixtures using g-computation to estimate the effect of simultaneously increasing the area under the receiver operating characteristic curve (AUC) for all PFAS. We identified 2 profiles: a higher PFAS profile (35% of sample) and a lower PFAS profile (relative to each other), based on their average PFAS concentrations at all time points. The higher PFAS profile had generally lower z scores for all outcomes, with somewhat larger effects for males, though all 95% CIs crossed the null. For example, the higher PFAS profile was associated with a 0.50-unit lower (ß = -0.50; 95% CI, -1.07 to 0.08) BMI z score among males but not among females (ß = 0.04; 95% CI, -0.45 to 0.54). We observed similar patterns with AUCs. We found that a higher childhood PFAS profile and higher cumulative PFAS mixtures may be associated with altered growth in early adolescence. This article is part of a Special Collection on Environmental Epidemiology.

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).

Body composition measures as a determinant of Alpelisib related toxicity.

BACKGROUND: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. METHODS: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, hospitalizations, time to treatment failure and overall survival. RESULTS: Sarcopenia was observed in half of the patients (n = 19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P = 0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P = 0.04) and hospitalizations (P = 0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. CONCLUSION: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.

The effects of dietary Spirulina platensis or curcumin nanoparticles on performance, body chemical composition, blood biochemical, digestive enzyme, antioxidant and immune activities of Oreochromis niloticus fingerlings.

CONTEXT: Recently, prioritize has been given to using natural phytogenic or nano compounds as growth promoters and immunostimulants in fish diets as an alternative to antibiotics. AIMS: The main propose of this trial was to determine the impact of supplementing diets with spirulina or curcumin nanoparticles on the performance and health indicators of Nile tilapia fingerlings. METHODS: In a 56-day feeding trial, 180 tilapia fingerlings were assigned into three main groups, as follows: 1st, control group, 2nd, Spirulina platensis (SP; 5 g kg-1 diet) and 3rd, curcumin nanoparticles (CUR-NPs; 30 mg kg-1 diet). KEY RESULTS: Incorporating tilapia diets with SP or CUR-NPs significantly improved performance, body chemical analysis, blood biochemical and hematological indices, digestive enzyme activities, and antioxidant and immunostimulant features compared to the control. CONCLUSION: Fortified tilapia diets with CUR-NPs or SP efficiently boost the productivity and health of Nile tilapia fingerlings. IMPLICATIONS: The research introduces new practical solutions for applying safe feed additives as alternatives to antibiotics in tilapia farming.

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition.

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

Growth performance, plasma metabolites, meat quality, and meat and lipid health indices of New Zealand White rabbits as affected by dietary dried tomato pomace powder supplementation during the summer season.

One hundred and twenty New Zealand White rabbits (NZW) (5-week-old; 735.27 ± 27.23 g) were kept in an open-sided house during the summer season. The experiment aims to evaluate the impacts of dried tomato pomace powder (DTPP) supplementation on rabbits' performance, blood metabolites, carcass traits, meat quality, and lipid and health indices of NZW rabbits during 5-13 weeks of age. The four treatments were a standard rabbit feed (control) and the control diet supplemented with 0.5, 1.0, and 1.5% DTPP, respectively. Rabbits fed a diet containing 1.5% DTPP showed the highest growth rate through weeks 9-13 of age despite having the lowest feed intake spanning 5-13 weeks. The best feed conversion ratio (FCR) was recorded in rabbits fed with 1.5% DTPP-supplemented diet for 5-13 weeks. Diets supplemented with 0.5 or 1.0% DTPP enhanced markedly dressing %, total edible flesh, saturated (SFAs), monounsaturated (MUFAs), and polyunsaturated fatty acid (PUFAs) contents, as well as the ∑n - 6/∑n - 3 ratio and the total n - 6 of meat. Dietary supplementation with DTPP decreased kidney, abdominal, and back fat. Diets supplemented with DTTP decreased total cholesterol, triglycerides, and very low-density lipoprotein (vLDL) concentrations. The greatest levels of linoleic acid, arachidonic and water-holding capacity in meat were observed in rabbits fed 1.5% DTPP-supplemented diets. Diets containing 1 and 1.5% DTPP improved meats' atherogenic and thrombogenic indices, meat lipid quality desired fatty acids/undesired fatty acids ratio, and meat health index. Conclusively, DTPP up to 1.5% maintained the growth performance of rabbits, boosted meat quality through increasing vitamin E, reduced fat deposition, modified fatty acid composition, and improved atherogenic, thrombogenic, and hypocholesterolemic indices of rabbit meat.

Impact of feeding biochar sources in rohu (Labeo rohita): Evaluating the growth, nutrient absorption, carcass composition, haematology and mineral status.

Biochar, an organic carbonaceous matter, is a unique feed additive that is now being used in aquaculture industry to formulate a cost-effective and eco-friendly diet. This experiment (in door) was conducted over course of 90 days to determine the most effective form of biochar, produced from various sources, for supplementation in Moringa oleifera seed meal-based diet. These sources were: farmyard manure biochar, parthenium biochar (PB), vegetable waste biochar, poultry waste biochar (PWB) and corncob waste biochar, added at 2 g/kg concentration to determine the effect of supplementation on the growth indices, nutrient absorption, carcass composition, haematology and mineral status of Labeo rohita (rohu) fingerlings. The research design consisted of six test diets with three replications (6 × 3) of each. Total of 270 fingerlings (6.30 ± 0.020 g) were fed at 5% body weight and 15 of them were kept in separate steel tanks. The results indicated that PWB was most effective in improving weight gain (285.58 ± 4.54%) and feed conversion ratio (1.060 ± 0.040) compared to control diet and other test diets. The same type of biochar (PWB) produced the best results for nutrient digestibility, that is, crude protein, crude fat and gross energy and carcass composition. In terms of haematology and mineral status, PWB showed the best results. In conclusion, it was found that PWB significantly enhanced (p < 0.05) L. rohita fingerling's growth, carcass composition, nutrient digestibility, haematological parameters (red blood cells, white blood cells, platelets and haemoglobin) and mineral composition (Ca, Na, P, Mg, Fe, Mn, Zn, K and Cu) whereas PB negatively affected all parameters. It is anticipated that the potential use of biochar will increase in aquaculture industry, as research on its incorporation in fish feeds is still limited.

Comprehensive analysis of body composition features in melanoma patients treated with tyrosine kinase inhibitors.

BACKGROUND: The introduction of tyrosine kinase inhibitors (TKI) has greatly improved the management of metastatic melanoma. Recent studies have uncovered a relationship between the body mass index (BMI) and outcome of patients with metastatic melanoma. However, conflicting results have challenged the relevance of this finding. In the current work, we aim to dissect body composition features of melanoma patients treated with TKI to evaluate their value as biomarkers. PATIENTS AND METHODS: We analyze body composition features via CT scans in a retrospective cohort of 57 patients with non-resectable stage III/IV melanoma receiving first-line treatment with TKI in our department, focusing on the impact of body composition on treatment efficacy and occurrence of adverse events. RESULTS: In uni- and multivariate analyses, we identify an association between the visceral adipose tissue gauge index (VATGI) and survival. We furthermore profile additional body composition features including sarcopenia, which was also associated with a shorter overall survival. Finally, we detected an enrichment of cases with fatigue in patients with low VATGI. CONCLUSIONS: Our study represents the first exploratory study evaluating the suitability of body composition measurements as biomarkers for melanoma patients treated with TKI. Our data suggest a putative use of VATGI as a biomarker predicting patient outcome.

Assessment of the potential effects of l-carnitine and cinnamon supplementation on weight loss and body composition.

OBJECTIVE: Aim: To assess efficacy of L-carnitine and cinnamon alone and in combination on body composition parameters in addition to compare between them. PATIENTS AND METHODS: Materials and Methods: Sample of 28 obese and overweight adults in Babylon city, sample collection includes patients in places, or by internet, where interview take place according to specialize questionnaire height, weight, and body mass index were measured. RESULTS: Results: A significant differences P<0.05 among gender distribution between male and female. A significant difference between (150-160 cm, 160-170 cm) as compared with (170-180 cm, 180-190 cm). A significant difference between 170-180 cm as compared with 180-190 cm but non-significant differences between 150-160 cm as compared with 160-170 cm. A significant difference between 26-35 as compared with 36-45, 46-55, but non-significant differences between 36-45 as compared with 46-55. A significant difference between body weight, body fat, water content, skeletal muscle, and body mass index after treatment, but non-significant differences between protein, and inorganic salt after treatment and at baseline. A significant difference between body weight, water content, skeletal muscle, and body mass index in group treated with cinnamon as compared with negative control group, but non-significant differences between body fat, protein, and inorganic salt as compared with negative control group. CONCLUSION: Conclusions: The prevalence of overweight and obesity within accepted range of that reported in Iraq, important relationship was reported between several life style risk factor, as soon as diagnose increase in weight and education health program for behavior of life style were high recommended.

Impact of 24-week dapagliflozin treatment on body weight, body composition, and cardiac risk indicators of patients with type-2 diabetes mellitus.

Background/aim: To reveal the impacts of dapagliflozin, a sodium glucose transporter-2 inhibitor (SGLT-2i), on body weight and body composition, cardiovascular risk indices, and carotid intima-media thickness (CIMT). Materials and methods: The data of patients with type-2 diabetes mellitus (T2DM) who applied to Department of Endocrinology and Metabolic Disorders between September 2019 and 2020, and had started dapagliflozin treatment along with their current medications were recorded retrospectively. Body weights, body compositions measured through bioelectrical impedance, and CIMT with T2DM receiving SGLT-2i treatment and medication were measured at weeks 1, 12, and 24 of 42. The visceral adiposity index (VAI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP) were used to determine the lipid measurements and anthropometric values. Results: The mean change in the total body weight and total fat mass was -2.96 and -1.97 kg, respectively (p < 0.001). There was a reduction in total fat mass of 1.23 kg (from 31.4 to 29.3 kg, p < 0.001) and in body fat percentage of 2.5% (from 35.8% to 34.4%, p < 0.001) in the first 12 weeks. A mild increase was observed in both the total fat mass and body fat percentage between weeks 12 and 24, which was not statistically significant (p = 0.783 and p = 0.925, respectively), whereas there was a statistically significant reduction in high-sensitive C-reactive protein (hsCRP), AIP, and CIMT values (p = 0.006, p = 0.035, and p = 0.007, respectively). No changes were observed in the VAI and LAP values (p = 0.985 and p = 0.636, respectively). Conclusion: It was observed that dapagliflozin not only contributes to weight and fat loss but also has positive impacts on cardiovascular and atherosclerotic indicators.

Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common noncommunicable diseases worldwide. The present study aimed to investigate the effects of oleoylethanolamide (OEA) supplementation combined with calorie restriction on inflammation, body composition, and hepatic fibrosis among obese patients with NAFLD. In this 12-week randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group. The weight-loss diet was also designed for both groups. Pre- and postintervention messenger RNA expression levels of the transcription factor nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and IL-10, body composition, and NAFLD fibrosis score were assessed. At the end of the study, the OEA group showed lower NF-κB and IL-6 expression levels compared to the placebo (p < .01). However, IL-10 expression level was approximately twofold higher in the OEA group compared to the placebo group (p = .008). A significant reduction was observed in the fat mass of the OEA group compared to the placebo (p = .044) postintervention. In addition, OEA supplementation led to a significant increase in fat-free mass in the OEA group compared to the placebo (p = .032). A remarkable increase was observed in resting metabolic rate (RMR) in the OEA group (p = .009); however, it was not found in the placebo group. There were no significant between-group differences in RMR postintervention. In addition, no significant within-and between-group differences were observed in the NAFLD fibrosis score at the end of the trial. Treatment with OEA along with weight-loss intervention could significantly improve inflammation and body composition in patients with NAFLD.

Saturated fat ingestion stimulates proatherogenic inflammation in polycystic ovary syndrome.

Inflammation and dyslipidemia are often present in polycystic ovary syndrome (PCOS). We determined the effect of saturated fat ingestion on circulating heat shock protein-70 (HSP-70) and mononuclear cell (MNC) toll-like receptor-2 (TLR2) gene expression, activator protein-1 (AP-1) activation, and matrix matalloproteinase-2 (MMP-2) protein in women with PCOS. Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity) participated in the study. HSP-70 was measured in serum and TLR2 mRNA and protein, AP-1 activation, and MMP-2 protein were quantified in MNC from blood drawn while fasting and 2, 3, and 5 h after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Androgen secretion was assessed from blood drawn while fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration. In response to saturated fat ingestion, serum HSP-70, TLR2 gene expression, activated AP-1, and MMP-2 protein were greater in lean women with PCOS compared with lean controls and in women with PCOS and obesity compared with controls with obesity. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects of their respective weight classes. Lipid-stimulated proatherogenic inflammation marker responses were negatively correlated with ISOGTT and positively correlated with abdominal adiposity and HCG-stimulated androgen secretion. In PCOS, saturated fat ingestion stimulates proatherogenic inflammation independent of obesity. This effect is greater when PCOS is combined with obesity compared with obesity alone. Abdominal adiposity and hyperandrogenism may perpetuate proatherogenic inflammation.NEW & NOTEWORTHY This paper demonstrates that in polycystic ovary syndrome (PCOS), ingestion of saturated fat triggers a molecular pathway of inflammation known to drive atherogenesis. This effect is independent of obesity as it occurs in lean women with PCOS and not in lean ovulatory control subjects. Furthermore, the combined effects of PCOS and obesity are greater compared with obesity alone.

Protein-carbohydrate interaction effects on energy balance, FGF21, IGF-1, and hypothalamic gene expression in rats.

Amino acids are involved in energy homeostasis, just as are carbohydrates and lipids. Therefore, mechanisms controlling protein intake should operate independently and in combination with systems controlling overall energy intake to coordinate appropriate metabolic and behavioral responses. The objective of this study was to quantify the respective roles of dietary protein and carbohydrate levels on energy balance, plasma fibroblast growth factor 21 (FGF21) and insulin growth factor 1 (IGF-1) concentrations, and hypothalamic neurotransmitters (POMC, NPY, AgRP, and CART). In a simplified geometric framework, 7-wk-old male Wistar rats were fed 12 diets containing 3%-30% protein for 3 wk, in which carbohydrates accounted for 30%-75% of the carbohydrate and fat part of the diet. As a result of this study, most of the studied parameters (body composition, energy expenditure, plasma FGF21 and IGF-1 concentrations, and Pomc/Agrp ratio) responded mainly to the protein content and to a lesser extent to the carbohydrate content in the diet.NEW & NOTEWORTHY As mechanisms controlling protein intake can operate independently and in combination with those controlling energy intakes, we investigated the metabolic and behavioral effects of the protein-carbohydrate interaction. With a simplified geometric framework, we showed that body composition, energy balance, plasma FGF21 and IGF-1 concentrations, and hypothalamic Pomc/Agrp ratio were primarily responsive to protein content and, to a lesser extent, to carbohydrate content of the diet.

Novel model to study the physiological effects of temporary or prolonged sex steroid deficiency in male mice.

Sex steroids are critical for skeletal development and maturation during puberty as well as for skeletal maintenance during adult life. However, the exact time during puberty when sex steroids have the highest impact as well as the ability of bone to recover from transient sex steroid deficiency is unclear. Surgical castration is a common technique to study sex steroid effects in rodents, but it is irreversible, invasive, and associated with metabolic and behavioral alterations. Here, we used a low dose (LD) or a high dose (HD) of gonadotropin-releasing hormone antagonist to either temporarily or persistently suppress sex steroid action in male mice, respectively. The LD group, a model for delayed puberty, did not show changes in linear growth or body composition, but displayed reduced trabecular bone volume during puberty, which fully caught up at adult age. In contrast, the HD group, representing complete pubertal suppression, showed a phenotype reminiscent of that observed in surgically castrated rodents. Indeed, HD animals exhibited severely impaired cortical and trabecular bone acquisition, decreased body weight and lean mass, and increased fat mass. In conclusion, we developed a rodent model of chemical castration that can be used as an alternative to surgical castration. Moreover, the transient nature of the intervention enables to study the effects of delayed puberty and reversibility of sex steroid deficiency.NEW & NOTEWORTHY We developed a rodent model of chemical castration, which can be used as an alternative to surgical castration. Moreover, the transient nature of the intervention enables to study the effects of delayed puberty and reversibility of sex steroid deficiency.

Effects of a novel polyphenol-rich plant extract on body composition, inflammation, insulin sensitivity, and glucose homeostasis in obese mice.

BACKGROUND/OBJECTIVES: The worldwide prevalence of obesity, metabolic syndrome and type 2 diabetes (T2D) is reaching epidemic proportions that urge the development of new management strategies. Totum-63 is a novel, plant-based polyphenol-rich active principle that has been shown to reduce body weight, fasting glycemia, glucose intolerance, and fatty liver index in obese subjects with prediabetes. Here, we investigated the effects and underlying mechanism(s) of Totum-63 on metabolic homeostasis in insulin-resistant obese mice. METHODS: Male C57Bl6/J mice were fed a high-fat diet for 12 weeks followed by supplementation with Totum-63 for 4 weeks. The effects on whole-body energy and metabolic homeostasis, as well as on tissue-specific inflammation and insulin sensitivity were assessed using a variety of immunometabolic phenotyping tools. RESULTS: Totum-63 decreased body weight and fat mass in obese mice, without affecting lean mass, food intake and locomotor activity, and increased fecal energy excretion and whole-body fatty acid oxidation. Totum-63 reduced fasting plasma glucose, insulin and leptin levels, and improved whole-body insulin sensitivity and peripheral glucose uptake. The expression of insulin receptor ß and the insulin-induced phosphorylation of Akt/PKB were increased in liver, skeletal muscle, white adipose tissue (WAT) and brown adipose tissue (BAT). Hepatic steatosis was also decreased by Totum-63 and associated with a lower expression of genes involved in fatty acid uptake, de novo lipogenesis, inflammation, and fibrosis. Furthermore, a significant reduction in pro-inflammatory macrophages was also observed in epidydimal WAT. Finally, a potent decrease in BAT mass associated with enhanced tissue expression of thermogenic genes was found, suggesting BAT activation by Totum-63. CONCLUSIONS: Our results show that Totum-63 reduces inflammation and improves insulin sensitivity and glucose homeostasis in obese mice through pleiotropic effects on various metabolic organs. Altogether, plant-derived Totum-63 might constitute a promising novel nutritional supplement for alleviating metabolic dysfunctions in obese people with or without T2D.

Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the study of women's health across the nation 1999-2018.

BACKGROUND/OBJECTIVES: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass, and proportion fat in midlife women. SUBJECTS/METHODS: This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women's Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0-18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition. RESULTS: After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P < 0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P < 0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P < 0.0001). PFOS was also significantly related to higher increase rates in WC (difference = 0.12% per year, P = 0.002) and fat mass (difference = 0.25% per year, P = 0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P < 0.0001), WC (P = 0.003), fat mass (P < 0.0001), and proportion fat (P = 0.0009). No significant results were found for PFNA. CONCLUSIONS: Certain PFAS were positively associated with greater body size and body fat, and higher rates of change over time. PFAS may be an underappreciated contributing factor to obesity risk.

A retrospective analysis of growth hormone therapy in children with Schaaf-Yang syndrome.

Short stature is a common phenotype in children with Schaaf-Yang syndrome (SYS). Prader-Willi syndrome (PWS) and SYS share several phenotypic features including short stature, muscular hypotonia and developmental delay/intellectual disability. Evidence exists that similar to PWS, growth hormone (GH) deficiency may also be a feature of SYS. Recombinant human GH (rhGH) therapy has been approved for PWS, but the effects of rhGH therapy in individuals with SYS have not yet been documented. This retrospective, questionnaire-based study analyzes the prevalence of rhGH therapy in children with SYS, the effects of rhGH therapy on anthropometric measures, and parental perception of the treatment. Twenty-six individuals with SYS were sent a clinical questionnaire and a request for growth charts. We found a significant increase in height z-score (p* = 0.04) as well as a significant decrease in body mass index 6 months after rhGH therapy initiation (p* = 0.04). Furthermore, height z-scores of the treated group (mean z-score = -1.00) were significantly higher than those of the untreated group (mean z-score = -3.36, p = 0.01) at time of enrollment. All parents reported an increase in muscle strength and endurance, and several families noted beneficial effects such as improved cognition and motor development.

Time-to-treatment window and cross-sex potential of ß2-adrenergic receptor-induced mitochondrial biogenesis-mediated recovery after spinal cord injury.

Mitochondrial dysfunction is a well-characterized consequence of spinal cord injury (SCI). We previously reported that treatment with the FDA-approved ß2-adrenergic receptor agonist formoterol beginning 8 h post-SCI induces mitochondrial biogenesis (MB) and improves body composition and locomotor recovery in female mice. To determine the time-to-treatment window of formoterol, female mice were subjected to 80 kdyn contusion SCI and daily administration of vehicle or formoterol (0.3 mg/kg) beginning 24 h after injury. This delayed treatment paradigm improved body composition in female mice by 21 DPI, returning body weight to pre-surgery weight and restoring gastrocnemius mass to sham levels; however, there was no effect on locomotor recovery, as measured by the Basso-Mouse Scale (BMS), or lesion volume. To assess the cross-sex potential of formoterol, injured male mice were treated with vehicle or formoterol (0.3 or 1.0 mg/kg) beginning 8 h after SCI. Formoterol also improved body composition post-SCI in male mice, restoring body weight and muscle mass regardless of dose. Interestingly, however, improved BMS scores and decreased lesion volume was observed only in male mice treated with 0.3 mg/kg. Additionally, 0.3 mg/kg formoterol induced MB in the gastrocnemius and injured spinal cord, as evidenced by increased MB protein expression and mitochondrial number. These data indicate that formoterol treatment improves recovery post-SCI in both male and female mice in a dose- and initiation time-dependent manner. Furthermore, formoterol-induced functional recovery post-SCI is not directly associated with peripheral effects, such as muscle mass and body weight.

Peripheral metabolic effects of ozone exposure in healthy and diabetic rats on normal or high-cholesterol diet.

Epidemiological studies show that individuals with underlying diabetes and diet-associated ailments are more susceptible than healthy individuals to adverse health effects of air pollution. Exposure to air pollutants can induce metabolic stress and increase cardiometabolic disease risk. Using male Wistar and Wistar-derived Goto-Kakizaki (GK) rats, which exhibit a non-obese type-2 diabetes phenotype, we investigated whether two key metabolic stressors, type-2 diabetes and a high-cholesterol atherogenic diet, exacerbate ozone-induced metabolic effects. Rats were fed a normal control diet (ND) or high-cholesterol diet (HCD) for 12 weeks and then exposed to filtered air or 1.0-ppm ozone (6 h/day) for 1 or 2 days. Metabolic responses were analyzed at the end of each day and after an 18-h recovery period following the 2-day exposure. In GK rats, baseline hyperglycemia and glucose intolerance were exacerbated by HCD vs. ND and by ozone vs. air. HCD also resulted in higher insulin in ozone-exposed GK rats and circulating lipase, aspartate transaminase, and alanine transaminase in all groups (Wistar>GK). Histopathological effects induced by HCD in the liver, which included macrovesicular vacuolation and hepatocellular necrosis, were more severe in Wistar vs. GK rats. Liver gene expression in Wistar and GK rats fed ND showed numerous strain differences, including evidence of increased lipid metabolizing activity and ozone-induced alterations in glucose and lipid transporters, specifically in GK rats. Collectively, these findings indicate that peripheral metabolic alterations induced by diabetes and high-cholesterol diet can enhance susceptibility to the metabolic effects of inhaled pollutants.