Search Results (740)

Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies. Full article

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Background: While epicardial adipose tissue (EAT) is a known predictor of adverse cardiovascular outcomes, lipomatous hypertrophy of the interatrial septum (LHIS) is composed of metabolically active fat such as brown adipose tissue, which may exert a different effect. This study investigates the coronary atherosclerosis profile in patients with LHIS using CTA, compared with a propensity score-matched control group. Methods: A total of 142 patients were included (n = 71 with LHIS and n = 71 controls) and propensity score-matched for age, gender, BMI, and the major CV risk factors (matching level, <0.05). CTA imaging parameters included HRP, coronary stenosis severity (CADRADS), and CAC score. Results: The mean age was 60.9 years +/− 10.6, there were nine (6.3%) women, and the mean BMI is 28.04 kg/m² +/− 4.99. HRP prevalence was significantly lower in LHIS patients vs. controls (21.1% vs. 40.8%; p < 0.011), while CAC (p = 0.827) and CADRADS (p = 0.329) were not different, and there was no difference in the obstructive disease rate. There was no difference in lipid panels (cholesterol, LDL, HDL, TG) and statin intake rate. Conclusions: HRP prevalence is lower in patients with LHIS than controls, while coronary stenosis severity and CAC score are not different. Clinical relevance: LHIS may serve as imaging biomarker for reversed CV risk. Full article

Background/Objectives: To investigate acute caffeine (CAF: 375 mg, ≈4.8 mg/kg body mass) effects on energy expenditure (EE) and substrate kinetics during high-intensity interval exercise in individuals with high (HBAT) versus low (LBAT) brown adipose tissue activity using time-trend polynomial modeling. Methods: This is a randomized, double-blind crossover study in which 35 highly-trained males [HBAT-CAF, HBAT-PLA (Placebo), LBAT-CAF, LBAT-PLA] performed 30-min treadmill HIIE. Infrared thermography (IRT) assessed BAT activity by measuring supraclavicular skin temperature (SST). Breath-by-breath ergospirometry measured EE (kcal/min) and carbohydrate (CHO), lipid (LIP), and protein (PTN) oxidation. We applied second- and third-order polynomial regression models to depict the temporal trajectories of metabolic responses. Results: HBAT groups showed 25% higher sustained EE versus LBAT (p < 0.001), amplified by CAF. CHO oxidation exhibited biphasic kinetics: HBAT had 40% higher initial rates (0.75 ± 0.05 vs. 0.45 ± 0.04 g/min; p < 0.001) with accelerated decline (k = −0.21 vs. −0.15/min; p = 0.01). LIP oxidation peaked later in LBAT (40 vs. 20 min in HBAT), with CAF increasing oxidation by 18% in LBAT (p = 0.01). HBAT-CAF uniquely showed transient PTN catabolism (peak: 0.045 g/min at 10 min; k = −0.0033/min; p < 0.001). Conclusions: BAT status determines EE magnitude and substrate-specific kinetic patterns, while CAF exerts divergent modulation, potentiating early glycogenolysis in HBAT and lipolysis in LBAT. The HBAT-CAF synergy triggers acute proteolysis, revealing BAT-mediated metabolic switching. Full article

Background/Objectives: Estrogen deficiency contributes to dyslipidemia and visceral adiposity, increasing cardiovascular risk in postmenopausal women. Sargassum fulvellum (Sf), a brown seaweed rich in bioactive compounds, possesses lipid-regulating properties that may be enhanced by lactic acid bacteria fermentation. This study aimed to evaluate the effects of fermented S. fulvellum (SfLlLm), prepared using Lactococcus lactis and Leuconostoc mesenteroides, on lipid metabolism and adipose tissue remodeling in an ovariectomized (OVX) mouse model of estrogen deficiency. Methods: Female C57BL/6 mice underwent ovariectomy and were fed an AIN-76A diet supplemented with either unfermented Sf or SfLlLm for eight weeks. Sham-operated and 17β-estradiol-treated OVX groups served as controls. Serum lipid levels—total cholesterol, triglycerides, LDL-C, and HDL-C—were assessed, and histological analysis of visceral adipose tissue was conducted to evaluate adipocyte morphology. Results: OVX-induced estrogen deficiency led to increased total cholesterol, triglycerides, and LDL-C, along with hypertrophic changes in visceral adipocytes. Supplementation with fermented Sargassum fulvellum (SfLlLm) markedly improved these parameters, reducing total cholesterol by 6.7%, triglycerides by 9.3%, and LDL-C by 52.9%, while increasing HDL-C by 17.5% compared to the OVX controls. SfLlLm also normalized visceral adipocyte size and distribution. These effects were comparable to or exceeded those of 17β-estradiol treatment. Conclusions: Fermented SfLlLm ameliorated dyslipidemia and visceral adiposity under estrogen-deficient conditions. These findings support its potential as a functional dietary intervention for managing postmenopausal lipid disorders and associated metabolic complications. Full article

The metabolic hyperactivity of tumor cells demands a substantial amount of energy and molecules to build new cells and expand the tumor, diverting these resources from healthy cells. Amino acids (AAs) are the only totipotent and essential molecules for protein construction. Previous in vitro studies in human and murine cancer cells, along with in vivo studies in mice, have shown that an excess of essential amino acids (EAAs) exerts an inhibitory effect on tumor proliferation by promoting apoptosis and autophagy. In this study, both in vitro and in vivo, we evaluated whether a mixture based on EAA can influence the development of human colon cancer (HCT116). To this end, in vitro, we assessed the proliferation of HCT116 cells treated with a special mix of EAA. In vivo, immunosuppressed athymic nude mice, injected with HCT116 cells subcutaneously (s.c.) or intraperitoneally (i.p.), were given a modified EAAs-rich diet (EAARD) compared to the standard laboratory diet (StD). In vitro data showed that the EAA mix impairs cancer growth by inducing apoptosis and autophagy. In vivo, the results demonstrated that EAARD-fed mice developed s.c. tumors significantly smaller than those of StD-fed mice (total mass 3.24 vs. 6.09 g, respectively). Mice injected i.p. and fed with EAARD showed a smaller and more limited number of intra-peritoneal tumors than StD-fed mice (total mass 0.79 vs. 4.77 g, respectively). EAAs prevents the growth of HCT116 cells by inducing autophagy and apoptosis, increasing endoplasmic reticulum stress, and inhibiting inflammation and neo-vascularization. In addition, the EAARD-fed mice, maintained muscle mass and white and brown adipose tissues. A diet with an excess of EAAs affects the survival and proliferative capacity of human colon cancer cells, maintaining anabolic stimuli in muscular cells. Full article

Obesity is not only an aesthetic problem but also an important comorbidity in metabolic syndrome and other types of pathologies. Currently discussed adjuvants are turmeric and curcumin, used as food supplements. Starting from synthesis in turmeric plant up to the use of turmeric as a spice, a significant amount of turmeric and its derivatives are lost during the processing procedure. In oral administration, the reduced bioavailability of these compounds must be taken into account, an aspect that can be improved by using different combinations and dosages. As for their pharmacodynamic effects, through its antioxidant and anti-inflammatory properties, curcumin improves mitochondrial function and promotes the browning of white adipose tissue. Another mechanism of action of curcumin in weight loss is enzymatic modulation, leading to a decrease in the activity of key enzymes involved in lipogenesis and an increase in the activity of lipolytic enzymes. These properties are enhanced by the synergistic action of the other polyphenols present in turmeric, especially calebin A, p-coumaric acid, caffeic acid and ferulic acid. Summarizing these effects, curcumin is a promising food supplement, opening new directions for further research to discover possibilities to improve or even eliminate the calamity of obesity that is currently wreaking havoc. Full article

The transforming growth factor beta (TGF-$\mathsf{\beta }$) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-$\mathsf{\beta }$ family genes based on the genome sequence in Tupaia belangeri, which were classified into the TGF-$\mathsf{\beta }$, bone morphogenetic protein (BMP), growth differentiation factor (GDF), glial cell-derived neurotrophic factor (GDNF), and Activin/Inhibin subfamilies. A phylogenetic analysis revealed the evolutionary relationships among members of the TGF-$\mathsf{\beta }$ family in T. belangeri and their homologous genes in Homo sapiens, Mus musculus, and Pan troglodytes, indicating a high degree of conservation throughout evolution. A chromosomal distribution and collinearity analysis demonstrated the localization of these genes within the genome of T. belangeri and their collinearity with genes from other species. A gene structure and motif analysis further illustrated the conservation and diversity among TGF-$\mathsf{\beta }$ family members. A protein interaction network analysis highlighted the central roles of TGFB1, TGFB3, BMP7, and BMP2 in signal transduction. A functional enrichment analysis underscored the significance of the TGF-$\mathsf{\beta }$ signaling pathway in the biological processes of T. belangeri, particularly in cell proliferation, differentiation, and apoptosis. We assessed the impact of cold acclimation treatment on the expression of TGF-$\mathsf{\beta }$ family proteins in the adipose tissue (white adipose tissue [WAT] and brown adipose tissue [BAT]) of T. belangeri using ELISA technology, finding that protein expression levels in the experimental group were significantly higher than those of in the control group. These results suggested that cold acclimation may enhance the adaptability of T. belangeri to cold environments by modulating the expression of TGF-$\mathsf{\beta }$ family genes. This study offers new insights into the role of the TGF-$\mathsf{\beta }$ family in the cold acclimation adaptation of T. belangeri, providing a scientific foundation for future genetic improvements and strategies for cold acclimation. Full article

Forskolin (FSK) induces the browning of white adipose tissue (WAT) through the activation of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) generation. When administered intravenously or orally, FSK undergoes significant metabolism and accumulation in the liver and other tissues, resulting in high side effects and low anti-obesity effects due to trivial amounts reaching WAT. This study examines the potential anti-obesity and metabolic effects of the inguinal WAT (IWAT) delivery of FSK in high-fat diet-induced C57BL/6J obese mice. Mice received one of the following treatments twice weekly for 4 weeks: 1. Control into both IWAT depots (Con^both); 2. FSK 15 mg/kg body weight (BW)/injection into both inguinal WAT (IWAT) depots (FSK15^both); 3. FSK 7.5 mg/kg BW/injection into both IWAT depots (FSK7.5^both); and 4. FSK 7.5 mg/kg BW/injection into the left IWAT depot (FSK7.5^left). Both the FSK15^both and FSK7.5^both treatments improved metabolic parameters by lowering blood glucose, enhancing glucose tolerance, and reducing serum insulin and cholesterol. The FSK15^both treatment had a greater impact on IWAT, resulting in smaller adipocytes and increased expression of Ucp1 and Tmem26 mRNA levels. All FSK treatments also reduced inflammatory and lipogenic markers in the liver, indicating improved hepatic metabolism. These findings suggest that local delivery of FSK into subcutaneous WAT is a potential strategy for combating obesity and improving metabolic health. However, further studies are needed to confirm the statistical and biological significance of these effects. Full article

Next to adrenergic signalling, purinergic pathways mediated by extracellular adenine nucleotides have been described to shape thermogenic and metabolic functions in brown adipose tissue (BAT). Here we describe high expression of P2X5 that is activated by ATP in mature adipocytes of BAT and differentiated brown adipocytes in vitro. The levels of other P2X family members were much lower, or expression was restricted to tissue-resident macrophages or endothelial cells. Global and brown adipocyte-specific P2rx5 deficiency resulted in lower expression of the uncoupling protein 1 (UCP1). However, indirect calorimetry studies showed that P2X5 did not affect systemic energy expenditure. Of note, glucose tolerance was impaired under chow and obesogenic high-fat diet conditions, which can be explained by lower glucose disposal into BAT but not into other organs. In summary, these data indicate a modulatory role of P2X5 in systemic and BAT-specific glucose metabolism. Full article

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues—pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential. Full article

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

Mulberry (Morus alba) twigs and leaves, rich in flavonoids, polyphenols, polysaccharides, and alkaloids with multi-target regulatory properties on glucose/lipid metabolism, were evaluated for their anti-obesity effects using methanol-extracted twigs (MTE) and aqueous-extracted leaves (MLE) in high-fat diet (HFD)-induced obese mice. Both extracts significantly ameliorated obesity-related metabolic dysregulation, as evidenced by attenuated body weight gain, visceral fat accumulation, serum lipid profiles, homeostatic model assessment of insulin resistance (HOMA-IR), and hepatic inflammation compared to HFD controls (p < 0.05). Concurrently, MTE and MLE enhanced systemic antioxidant capacity and elevated high-density lipoprotein cholesterol (HDL-C) levels. Notably, high-dose MTE (MTEH, 1000 mg/kg) markedly reduced perirenal adiposity while increasing brown adipose tissue mass (p < 0.05). Mechanistic investigations revealed that MTEH reshaped gut microbiota composition by suppressing Firmicutes and Enterococcus, while enriching beneficial Faecalibaculum and Bifidobacterium spp. (p < 0.05). Furthermore, cecal short-chain fatty acid (SCFA) profiling demonstrated MTEH and MLEH-mediated metabolic reprogramming, characterized by increased propionic acid and decreased butyric acid, suggesting microbiota-dependent modulation of host energy metabolism. These findings collectively highlight the potential of mulberry extracts as multi-targeted nutraceuticals for obesity intervention via gut microbiota–SCFA axis regulation. Full article

The purpose of this study was to determine the effects of essential oil inhalation on body weight, blood lipid profile, and liver and adipose tissue in mice. Middle-aged male mice (C57BL/6J) were exposed to Lavandula angustifolia (LO) and Citrus aurantium (CAO) essential oils for 7 weeks and compared to mice that did not receive essential oil inhalation treatment. Liver, white adipose tissue, and brown adipose tissue were sampled, kept at −80 °C. Although essential oil inhalation increased feed intake and body weight compared to control group, the amount of weight gain per feed intake was lower in the C. aurantium essential oil group. Moreover, relative weight of fat to body weight, liver fat amount, and blood cholesterol was lower, and triglyceride levels were significantly reduced. Reverse transcription polymerase chain reaction (RT-PCR) expression profiling of genes related to lipid metabolism confirmed changes in the regulation of thermogenesis-related gene Ucp1 and the cholesterol synthesis-related genes Hmgcs1 and Hmgcr. The inhalation of C. aurantium essential oil did not reduce the feed intake in mice; however, its effectiveness in suppressing the increases in body weight and fat mass was demonstrated. Full article

C-phycocyanin (CPC), a bioactive compound derived from Spirulina, has been described as a molecule with antioxidant and anti-inflammatory properties. It has also been demonstrated that sustainably obtained CPC effectively inhibited body mass gain, regulated serum leptin and resistin levels, and prevented the onset of a pro-inflammatory state in Swiss mice fed a hyperlipidic diet. These results highlighted the anti-obesogenic potential of CPC. Brown adipose tissue (BAT) has been identified as a promising target in the treatment of obesity, playing a role in energy expenditure. In this study, Swiss mice fed a high-fat diet were supplemented with 500 mg/kg body weight of CPC daily for 12 and 16 weeks. BAT was collected, and Western blot and ELISA were performed. A reduction in pro-inflammatory cytokines, as well as a decrease in leptin levels was observed in the tissue, which was also associated with a reduction in BAT relative weight to body mass. Furthermore, CPC administration was able to modulate uncoupling protein 1 (UCP1) levels, which is crucial in the thermogenesis process. Therefore, this study demonstrated that supplementation with CPC reduces inflammatory cytokines associated with detrimental effects in the BAT, emerging as a tool in combating obesity and improving BAT function. Full article