Obesity is a global pandemic that affects people of all ages. While behavioral, nutritional, and socioeconomic factors all contribute to weight gain, other factors in our immediate environment play an insidious role in the prevalence of obesity. Exposure to environmental and pharmaceutical compounds can be a contributing factor to increased weight gain. Using the zebrafish obesogenic test, our study demonstrates that amiodarone, dibutyl phthalate, rosiglitazone, tributyltin, and triclosan induce a thrifty phenotype under short-term fasting conditions. Diazepam significantly reduces locomotion without exhibiting any obesogenic effect, whereas tributyltin, which has the highest obesogenic potential among the tested compounds, has no effect on locomotion. The obesogen-induced resistance to fat loss is not correlated to inhibition of physical activity and a corresponding reduction in energy expenditure, nor to food consumption. Primary prevention measures to fight against the obesity pandemic may include reducing exposure to obesogens that can induce a thrifty phenotype.

Association between facial lipoatrophy and self-esteem in people living with HIV/AIDS on antiretroviral therapy in Brazil: A cross-sectional study.

High fat diet (HFD) and associated obesity are suggested to predispose to cancer development, complicate cancer treatment, and accelerate mortality. Paradoxically, obese patients with lung cancer are reported to live longer, suggesting that high body mass is protective. Given that cachexia-tumor-induced weight loss with adipose and muscle wasting-is prevalent in lung cancer, we speculated that obese patients might survive longer due to the protective effect of larger tissue reservoirs, slowing time to fatal wasting. Thus, we modeled this condition using lean and high fat diet (HFD)-induced obese mice with Lewis lung carcinoma (LLC) tumors versus non-tumor bearing controls. We also assessed the effects of feeding HFD to lean mice with and without LLC tumors. HFD and obese-HFD without tumors gained weight over the study, with obese HFD mice exhibiting low muscle mass with obesity at endpoint. Low fat diet (LFD)-fed lean mice with LLC tumors (LFD-LLC) showed no change in total body weight, but exhibited reduced skeletal muscle, heart, and fat pad mass along with hepatosplenomegaly at endpoint. HFD and pre-existing obesity both modified the response to Lewis lung carcinoma (LLC) tumors. HFD did not affect tumor-induced weight loss, fat loss, or tumor burden, but worsened loss of gastrocnemius, tibialis anterior, and heart muscle, prevented hepatosplenomegaly, and enhanced tumor cell proliferation and expression of the cachexia-inducing cytokine, Interleukin-6 (IL-6). Obese-HFD mice showed greater tumor burden versus LFD and the worst cachexia phenotypes, including greater weight loss and muscle loss than HFD or LFD. This worsened cachexia was associated with increased blood-born inflammatory cytokines, increased phosphorylated STAT3 in muscle, and increased IL-6 expression in muscle, spleen, and tumor. Obese-HFD was associated with the highest rate of tumor cell proliferation in vivo and serum from obese HFD mice increased LLC cell proliferation in vitro. Thus, HFD and pre-existing obesity each separately enhance inflammation, cachexia, and tumor growth. These distinct contributions of HFD and chronic adiposity are potential therapeutic targets to slow cachexia and tumor growth in cancer.

Insulin and adipocyte IRF4 promote fat retention over muscle preservation during intermittent fasting in obesity.

Abstract Introduction Postmenopausal osteoporosis, defined by reduced bone mineral density and fracture risk, is a major health concern. Bisphosphonates are standard therapy, but the added value of exercise is uncertain. This study examined their combined effects on BMD, bone turnover, body composition, strength, and balance in postmenopausal women. Content PubMed, Embase, and Cochrane Central were systematically searched for RCTs on bisphosphonates, exercise, or their combination in postmenopausal osteoporosis. Primary outcomes were changes in BMD at lumbar spine, femoral neck, and total hip. Secondary outcomes included bone turnover markers (ALP-B, NTx), body composition (fat and lean mass), and leg extensor strength. Study quality was assessed with Cochrane Risk of Bias tool. Mean differences with 95 % confidence intervals (CI) were calculated using a random-effects model, with heterogeneity evaluated by I 2 . Summary Six RCTs with 1,059 subjects qualified for inclusion. Bisphosphonate + exercise treatment showed small and non-significant improvement in lumbar spine and femoral neck BMD (p=0.41 and p=0.11, respectively), and no significant change in total hip BMD (p=0.48). Levels of ALP-B significantly increased (p=0.0008), reflecting bone turnover rather than a direct clinical benefit; NTx showed non-significant trend (p=0.10). Fat mass significantly decreased (p<0.00001), leg strength significantly increased (p<0.00001), and lean mass showed no significant change (p=0.14). Outlook Combined exercise and bisphosphonates yield modest yet consistent improvements in site-specific BMD, fat loss, and strength in postmenopausal osteoporosis, supporting exercise as an adjunct to pharmacologic therapy for musculoskeletal health.

Background.GLP-1 receptor agonists (GLP-1RAs) are central to obesity pharmacotherapy, producing substantial and sustained weight loss in randomized trials, with additional cardiometabolic benefits. Growing attention concerns their effects on body composition, particularly fat versus lean mass loss, and potential impacts on skeletal muscle function and physical performance. These outcomes are highly relevant to sports medicine and rehabilitation, where muscle preservation is crucial. Aim.To review evidence on the effects of GLP-1RAs on body composition and physical performance in adults with obesity, focusing on fat mass, lean mass and populations at risk of muscle-related adverse effects. Materials and methods.Narrative review of 30 PubMed-indexed studies (2015–2026), including RCTs, DXA substudies and reviews of liraglutide, semaglutide and tirzepatide in adults with overweight/obesity. Results.GLP-1RAs consistently reduced body weight and fat mass, with 15–40% of weight loss attributable to lean mass reduction. Semaglutide improved physical function and exercise tolerance in obesity-related functional impairment and HFpEF, while potential sarcopenic effects were reported in older adults and those with low baseline muscle mass. Reviews highlight heterogeneity of lean mass responses and the importance of lifestyle interventions. Conclusions.GLP-1RAs induce major fat loss but are associated with clinically relevant lean mass loss. Combining pharmacotherapy with exercise and nutrition is essential to optimize body composition and physical performance.

Introduction: Diet and exercise interventions reduce the risk of obesity; however, fat loss varies across individuals. During moderate-intensity aerobic exercise, norepinephrine stimulates adipose lipolysis via β3-adrenergic receptors (β3AR). The β3AR Trp64Arg polymorphism has been linked to reduced lipolytic responsiveness. This study examined whether Trp64Arg influences fat breakdown during aerobic exercise in young women. We hypothesized that Trp64Arg carriers (Trp/Arg) would show a blunted rise in circulating free fatty acids (FFA) and higher respiratory quotient (RQ; VCO₂/VO₂) during exercise than that of non-carriers (Trp/Trp). Methods: Thirty-seven healthy female university students (20–23 years) completed 40 min of cycling at 55 W after a standardized dinner and 12-h fast. Serum FFA, energy expenditure, and RQ were measured at rest and during exercise. Participants were genotyped and classified as wild-type (Trp/Trp; n = 29) or heterozygous (Trp/Arg; n = 8). Repeated-measures analyses tested group, time, and group × time effects; estimated marginal means were used for model-based summaries. Results: Serum FFA at 40 min increased compared to that of rest in both groups, but reached significance only in the wild-type group (2.04 ± 1.25 vs 0.90 ± 0.48 mEq/L, p = 0.009). During exercise, RQ differed according to genotype (main effect of group: p = 0.003; group × time: p = 0.065), with higher RQ in heterozygous participants (0.91 ± 0.02, 95% CI 0.88–0.94) than in the wild-type group (0.86 ± 0.01, 95% CI 0.84–0.88). Conclusions: In young women, carrying the Trp64Arg polymorphism of the β3AR gene potentially contributes to a blunted lipolytic response and relatively high reliance on carbohydrate metabolism during moderate-intensity aerobic exercise.

Background: Type 2 diabetes (T2D) increases cardiovascular disease (CVD) risk and predisposes individuals to heart failure with preserved ejection fraction. Metabolic dysfunction-associated steatotic liver disease (MASLD), prevalent in T2D, may worsen cardiac remodelling and haemodynamics. This secondary analysis of the DIASTOLIC trial examined the relationship of liver fat to cardiac remodelling in T2D at baseline and after a 12-week intervention or standard care. Methods: Adults with obesity and T2D and matched controls underwent hepatic MRI, cardiac MRI, echocardiography, and adipokine profiling as part of the DIASTOLIC study (NCT02590822). Participants with T2D were randomised to supervised exercise, a low-calorie meal-replacement plan (MRP), or routine care for 12 weeks. A baseline case–control and then pre- and post-analyses in those with T2D were performed. Associations between changes in liver fat and cardiovascular measures were assessed using correlation and adjusted generalised linear models. Results: At baseline, 81 T2D and 35 healthy controls were compared, and 76 subjects with T2D completed the trial. Participants with T2D had ~4× higher hepatic fat and adverse haemodynamics. The MRP arm achieved the greatest reductions in BMI, blood pressure, dysglycaemia, insulin resistance, and hepatic fat (−8.9%), with favourable adipokine changes. Overall, hepatic fat loss was associated with reductions in cardiac index and stroke volume and with additional reductions in end-diastolic volume in the MRP arm, independent of BMI. Conclusions: In T2D, hepatic fat is strongly linked to pathological haemodynamic profiles. Intensive caloric restriction achieves substantial hepatic fat loss and normalisation of hyperdynamic cardiovascular physiology independent of weight loss, identifying hepatic steatosis as a potential therapeutic target for early cardiovascular risk reduction.

Association of Fat and Muscle Mass With Overall Survival in Patients With Metastatic Prostate Cancer Treated With Enzalutamide, Abiraterone, and Docetaxel.

Tumor-immune-neural circuit disrupts energy homeostasis in cancer cachexia.

Differential effects of the anti-obesity drug tirzepatide on adipose tissues: Brown fat as a key target.

Pericardial and interstitial alcianophilic gelatinous degeneration in anorexia nervosa.

ABSTRACTPurposeRheumatoid cachexia has been described as a process of concurrent muscle loss and gain of adipose tissue. We evaluated longitudinal changes in body composition in patients with rheumatoid arthritis (RA) to evaluate the changes in adiposity that accompany loss of lean mass.MethodsWe combined and assessed three independent longitudinal RA cohorts that included assessments of body composition. Whole body DXA was performed in all participants to quantify appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2). Independent associations between loss of ALMI during follow‐up and FMI over the same time‐period were assessed adjusting for age, sex, race, baseline body composition and study using mixed‐effects regression to account for clustering by study. Changes in adipokines (adiponectin and leptin) were also assessed over time in similar models. Visceral fat area was determined from DXA (cm2) in one of the cohorts and was also assessed.ResultsAmong 451 patients with a mean (SD) age of 58.3 (10.5), the mean (SD) ALMI was 6.97 (1.41) kg/m2. Longitudinal analyses were conducted in 361 participants with follow‐up data [average follow‐up 2.65 (0.71) years]. Of these, 195 lost lean mass (experienced a negative change in ALMI during follow‐up), while 166 gained lean mass. Participants that lost lean mass had greater reductions in BMI [−0.77 (95% CI: −1.21, −0.33) v. +1.07 (95% CI: 0.56, 1.59)], greater reductions in FMI [−0.17 (95% CI: −0.48, 0.14) v. +0.46 (95% CI: 0.08, 0.83) p = 0.07] and a greater odds of having a reduction in FMI [OR: 2.30 (1.31, 4.05) p = 0.004], and had declining leptin levels and visceral fat area. Associations were strongest among those with high FMI at baseline.ConclusionsIn RA, loss of lean mass tends to occur in the context of a loss of weight and a loss of both total and visceral adiposity. These observations help to inform our understanding of the mechanisms leading to loss of muscle and rheumatoid cachexia in RA as well as to inform potential screening practices.

Dual intestinal-hepatic modulation by phenolic acids improves metabolic-dysfunction associated steatohepatitis.

Distinct effects of ketogenic and non-ketogenic weight-loss diets on hepatic steatosis and mitochondrial metabolism in MASLD.

Menopause represents a significant physiological transition characterized by decreased ovarian hormones, including estrogen and progesterone, accompanied by metabolic changes such as increased visceral adiposity, weight gain, insulin resistance, and higher cardiometabolic risk. Intermittent fasting, defined as alternating periods of fasting and eating, has been studied as a nutritional strategy for weight management and metabolic improvement in adults, including perimenopausal and postmenopausal women. Recent systematic reviews and meta-analyses indicate that intermittent fasting may reduce fasting glucose, insulin resistance, waist circumference, and inflammatory markers, while promoting body fat loss, although specific evidence in menopausal women remains limited. Potential risks include lean mass loss, nutritional deficiencies, and reduced bone density, particularly when undertaken without professional supervision. In conclusion, intermittent fasting shows potential metabolic benefits in menopausal women, but clinical implementation should be individualized and evidence-based, under professional guidance.

Cancer cachexia is a syndrome characterized by significant weight loss, particularly of adipose tissue, which negatively impacts patient survival. Pharmacological approaches to prevent this abnormal fat reduction remain poorly defined. This study investigated the potential of ellagic acid (EA) to mitigate cancer-induced fat loss. In vitro, 3T3-L1 adipocytes were exposed to 50% conditioned medium (CM) from CT26 colon cancer cells to mimic cachectic conditions. The effects of EA on lipid accumulation and adipogenesis-related markers (PPARγ and RXRβ) were analysed. The mechanism was validated using molecular docking and siRNA-mediated gene silencing. Invivo, a cachexia mouse model was established by subcutaneous injection of CT26 cells into BALB/c mice. Mice were orally administered EA at dose of 10, 20 and 40 mg/kg, respectively (n = 7 per group) for 14 days to evaluate its protective effects. In 3T3-L1 cells, the 50% CM-treatment reduced lipid accumulation by 14% (p < 0.05) and downregulated PPARγ (p < 0.05) and RXRβ (p < 0.01) expression. The EA treatment restored diminishedlipid levels and rescued downregulated the expression of PPARγ (p < 0.05) and RXRβ (p < 0.01). This pro-adipogenic effect was abolished by siRNA-mediated inhibition of RXRβ. In the cachexia mouse model, EA treatment significantly improved physical performance and body composition. Specifically, EAenhanced grip strength by 1.32-fold (10 mg/kg, p < 0.0001) and 1.24-fold (20 mg/kg, p < 0.001), increased the inguinal white adipose tissue (iWAT) mass by 59.8% (10 mg/kg, p < 0.01), and 56.1% (20 mg/kg, p < 0.05), and was accompanied by a significant increase in the tumour-free body weight of 6.4% (10 mg/kg, p < 0.05), and 5.6% (20 mg/kg, p < 0.01) compared to cachectic mice. EA treatment did not affect tumour growth. It increasedthe adipogenesis-related protein expression of C/EBPα (2.1-fold, p < 0.05), PPARγ (1.5-fold, p < 0.05) and SREBP1 (1.5-fold, p < 0.05) in the iWAT. The EA treatment enhanced the nuclear localization index of RXRβ in the iWAT by 0.51 (10 mg/kg, 1.9-fold, p < 0.05) and 0.46 (20 mg/kg, 1.7-fold, p < 0.05) compared to cachectic mice. EA mitigates cancer cachexia-induced fat loss by the activation of the RXRβ-PPARγ pathway. These findings present EA as a potential pharmacological agent to improve the abnormal fat reduction and muscle dysfunction associated with cachexia.

The impact of exercise self-efficacy, self-esteem and physical activity on body fat percentage changes in adolescents during fat loss interventions.

Effective anti-obesity interventions that preserve lean mass are of increasing clinical significance for optimizing metabolic health. This study investigated whether lorcaserin, a centrally acting weight loss agent, modifies body composition, circulating lipidomic profiles, and muscle-regulating hormones within the myostatin-activin-follistatin-IGF-1 (MAFI) axes. Forty-eight adults with obesity were randomized to lorcaserin (10 mg twice daily) or placebo for 6 months in a double-blind trial. Regional body composition, hormones and lipidomics were assessed. Changes were analysed using linear mixed models with fixed effects for time, treatment and interaction. Adjusted deltas and endpoints were compared by analysis of covariance controlling for baseline body mass index. Lipidomic profiles were analysed using principal component and partial least-squares discriminant analyses. Lorcaserin reduced total body weight (time*treatment, p = 0.004). Adjusted delta and endpoint comparisons showed reductions in total body (p = 0.031) and abdominal fat mass (p = 0.002). Lipidomic assessments revealed primarily lower levels of triglyceride-rich lipoproteins with treatment. No significant changes in MAFI axes components were detected in linear mixed models. Lorcaserin treatment was associated with greater abdominal fat mass loss, favourable lipid profile changes, while MAFI components remained largely unaffected. Lorcaserin may improve cardiometabolic health primarily through reductions in central adiposity.

Introduction and Purpose. Obesity is a major global health challenge, requiring effective long-term treatments. Liraglutide, a GLP-1 agonist, is effective for weight loss and reducing visceral fat. However, its impact on lean body mass (LBM) and muscle mass is crucial, as their loss can lead to sarcopenia, metabolic impairment, and weight regain. Therefore, this literature review systematically analyses liraglutide's effects on LBM and muscle mass in obesity and/or type 2 diabetes, and presents strategies to minimise potential muscle loss during therapy. Materials and methods. A systematic review of the scientific literature was conducted. Literature available in the PubMed and Google Scholar databases was searched using keywords. Results. The findings from clinical trials are not definitive. While several studies report a statistically significant loss of lean body mass (LBM), it remains proportionally smaller than fat loss and may constitute up to 40% of total weight reduction. Conversely, other studies—including the most recent ones—indicate that liraglutide primarily reduces adipose tissue. This effect preserves LBM and can enhance muscle quality by reducing intramuscular fat. The observed absolute decrease in LBM appears strongly correlated with total weight loss, implying it is a consequence of weight reduction itself rather than a specific drug-induced catabolic effect. Preliminary data also suggest liraglutide may have a direct anabolic and protective effect on skeletal muscle via modulation of signalling pathways. To mitigate muscle loss, pharmacotherapy should be combined with non-pharmacological interventions, such as a high-protein diet (1.2–1.6 g/kg bw/day) and regular resistance training. Combination therapies including anabolic agents also represent a promising approach.