Search Results (654)

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. Full article

Background: The UCP1 A-3826G polymorphism, located in the gene’s regulatory region, is associated with obesity and altered fat metabolism. Because UCP1 plays a central role in thermogenesis, variation in its expression may influence metabolic efficiency and dietary fat preference. Methods: We examined associations between the A-3826G polymorphism and food preferences in healthy young Japanese adults (50 males, 48 females). Preferences for high-fat and basic-taste foods were assessed using a self-administered questionnaire, with sweet foods classified as low- or high-fat. Genotypes (AA, AG, GG) were analyzed using a two-way mixed-design ANOVA to evaluate genotype × fat level interactions. Results: Preference scores for basic tastes did not differ significantly among genotypes in either sex (except for sour taste in males). In males, no significant genotype × fat level interaction was observed, although AA carriers preferred high-fat to low-fat sweet foods (p < 0.05). In females, a significant genotype × fat level interaction was detected (p < 0.01), with AG carriers showing lower preference for high-fat sweet foods. Conclusions: These findings indicate that the UCP1 A-3826G polymorphism may modulate preference for high-fat sweet foods in a sex-dependent manner, suggesting a link between thermogenic genetic variation and dietary fat preference relevant to obesity prevention. Full article

Obesity is characterized by abnormal adipose tissue expansion and energy metabolism imbalance. Browning of white adipose tissue (WAT), wherein white adipocytes acquire thermogenic properties similar to brown adipose tissue, represents a key mechanism for increasing energy expenditure. Although ginseng (Panax ginseng C.A. Meyer) is widely recognized as a health-promoting botanical, its role in WAT browning has not been fully elucidated. This review summarizes evidence that ginseng and its bioactive components regulate major thermogenic pathways, including β-adrenergic/cyclic adenosine monophosphate-protein kinase (cAMP-PKA) signaling, AMP-activated protein kinase (AMPK), and the peroxisome proliferator-activated receptor γ (PPARγ)/coactivator 1α (PGC-1α) axis, thereby upregulating key markers such as uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and type II iodothyronine deiodinase (DIO2). These effects promote mitochondrial function and fatty acid oxidation, reduce lipogenesis, alleviate inflammation, and improve insulin sensitivity, collectively fostering a microenvironment conducive to browning. Furthermore, fermentation has been found to enhance the bioactivity and thermogenic efficacy of ginseng. Recent evidence indicates that gut microbiota and their metabolites—such as short-chain fatty acids, unsaturated fatty acids, and bile acids—play a notable role in ginseng-induced thermogenesis via receptors including G-protein-coupled receptor 41/43 (GPR41/43), takeda G-protein-coupled receptor 5 (TGR5), and farnesoid X receptor (FXR). These multi-organ interaction networks involving the gut–fat, gut–liver, and gut–brain axes reflect the role of ginseng in integrating systemic metabolism. In summary, this review discusses the multi-level regulatory network through which ginseng promotes WAT browning, providing a mechanistic basis for its potential application in body weight and metabolic health management. Full article

Obesity is a chronic metabolic disorder characterized by excessive accumulation of body fat and is a major risk factor for various diseases, including type 2 diabetes, hypertension, and cardiovascular diseases. This study investigated the anti-obesity effects of cannabigerol-dominant C. sativa inflorescence extracts (CEs) obtained using various ethanol concentrations. The extracts were analyzed by UPLC to determine their major components. Additionally, anti-obesity mechanisms of the extracts were further determined through RT-qPCR and Western blot analysis to evaluate gene and protein expression levels. A total of seven cannabinoids, including cannabigerol as a major constituent, were identified within CE. Differentiation of 3T3-L1 cells was dose-dependently inhibited by CE at all ethanol concentrations. Furthermore, the gene and protein expression levels of key adipogenic and lipogenic markers, such as PPARγ, C/EBPα, SREBP-1c, and FAS, were significantly downregulated by CE treatment. In contrast, the expression of factors involved in lipolysis and white adipose tissue browning, such as HSL, ATGL, UCP1, and PGC-1α, was markedly increased by CE treatment. These effects were enhanced in an ethanol concentration-dependent manner. In conclusion, these results demonstrate that cannabigerol-dominant C. sativa effectively mitigates obesity by suppressing adipogenesis and lipogenesis while concurrently stimulating lipolysis and white adipose tissue browning. Full article

Sunite sheep are well-adapted to the cold Mongolian steppe, exhibiting robust metabolic flexibility in which adipose tissue contributes significantly to energy homeostasis. Proteomics analysis of scapular fat in Sunite sheep during winter and summer identified 432 upregulated and 493 downregulated differentially expressed proteins (DEPs). These DEPs were notably enriched in essential biological functions such as energy metabolism, lipogenesis, and thermogenesis. Furthermore, they exhibited significant enrichment of signaling pathways such as oxidative phosphorylation and fatty acid metabolism. Meanwhile, the precursor protein of asprosin (ASP),profibrillin-1 (pFBN1), showed a marked decrease during winter. Given that ASP had been demonstrated to exert metabolic regulatory effects promoting lipid synthesis and suppressing thermogenesis in model animals, it was hypothesized that the seasonal downregulation of pFBN1 might drive adaptive thermogenesis through ASP. Therefore, this study focused on functional validation of the ASP-encoding gene FBN1 (fibrillin-1). In Adipose-Derived Mesenchymal Stem Cells (ADMSCs), FBN1 was specifically downregulated through overexpressing of its regulatory factor miR-29b-1. The results indicated that downregulation of the FBN1 led to the inhibition of adipogenesis in ADMSCs. This was reflected by a reduction in the number of lipid droplets, a decrease in the expression of adipogenesis marker genes, and a significant drop in triglyceride levels. Furthermore, the reduction in FBN1 levels enhanced the thermogenic function of differentiated adipocytes derived from ADMSCs, as evidenced by enhanced expression of thermogenic marker genes, along with a notable rise in both uncoupling protein 1 (UCP1) and non-esterified fatty acid (NEFA) levels. Full article

Thermoregulatory dysfunction is a major pathophysiological consequence of aging, affecting many elderly individuals. Growth hormone secretagogue receptor (GHSR) regulates energy homeostasis and immune function. We previously showed that global GHSR deletion improves thermogenic adaptation of brown adipose tissue (BAT) in aging, but the responsible cell type remained unclear. GHSR is expressed in macrophages, and its expression in macrophages increases with aging. Here, we studied myeloid-specific Ghsr-deleted male mice (LysM-Cre; Ghsr^f/f denoted as “KO”) to assess their metabolic and immune responses to cold stress at young and old ages. Old mice showed impaired thermogenesis, marked by reduced core body temperature under 4 °C cold exposure, a blunted cold-induced increase in glucose levels, reduced BAT mass, and increased infiltration of pro-inflammatory CD38⁺ macrophages in BAT. In contrast, KO mice exhibited enhanced cold tolerance in both young and old mice. Notably, aged KO mice showed preserved BAT mass and a pronounced shift in resident macrophages toward an anti-inflammatory state. Consistently, aged KO mice showed reduced pro-inflammatory markers (Ccl2, Nos2) and increased expression of the thermogenic gene Ppargc1a and UCP1 protein under cold exposure. Together, these findings demonstrate that macrophage GHSR drives age-associated pro-inflammatory remodeling of BAT, and that its deletion promotes an immune environment favorable for thermogenic activation. Thus, targeting macrophage GHSR may offer a new therapeutic strategy to restore thermogenesis and enhance thermal resilience in aging. Full article

Doxorubicin (Dox)-induced cardiotoxicity (DIC) was characterized by severe myocardial damage that might progress to irreversible heart failure. There were limited options available for the prevention and treatment of DIC. Chicory (Cichorium intybus L.) has demonstrated notable cardioprotective effects. However, its potential to mitigate DIC remains unexplored. This study aimed to assess the therapeutic potential of chicory in alleviating DIC and elucidate its active ingredients and potential molecular mechanism. Male Sprague-Dawley (SD) rats were used to construct DIC models. The rats were prophylactically gavaged chicory to evaluate the therapeutic effect of chicory on DIC. The UPLC-QExactivePlus system was used for the subsequent analysis of heart tissue samples to reveal the potential active ingredients of chicory. The binding of chicory components to uncoupling protein 2 (UCP2) and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) was validated using surface plasmon resonance (SPR). Highly binding ingredients were then utilized in an H9c2 cell model to validate underlying mechanisms. Chicory alleviated Dox-induced cardiac dysfunction and myocardial structural injury, and reversed mitochondrial damage. These protective effects may be attributed to its activation of UCP2 and inhibition of NLRP3 signaling, thereby attenuating Dox-induced cardiac oxidative damage and inflammatory infiltration. Additionally, a total of 15 chemical compositions of chicory into rat heart tissue were characterized. SPR validation demonstrated that nine compounds targeting UCP2 and NLRP3 increased survival rates in Dox-induced H9c2 cells, reduced oxidative and inflammatory levels, and improved mitochondrial function. Chicory could effectively alleviate DIC by reducing oxidative stress, inflammation, and preserving mitochondrial function. These findings offer a novel insight into chicory’s clinical relevance in DIC management. Targeting UCP2 to regulate the NLRP3 pathway highlights chicory as a promising therapeutic strategy for preventing and treating DIC. Full article

Cancer is a multifactorial disease influenced not only by genetic and epigenetic alterations but also by interactions with the surrounding microenvironment. Among the hallmarks of cancer, metabolic reprogramming enables tumor cells to adapt and survive under adverse conditions. These metabolic alterations also induce changes in stromal cells. In clear cell renal cell carcinoma (ccRCC), adipocytes are among the most abundant stromal components. We have previously shown that ccRCC progression depends on the bidirectional crosstalk between tumor epithelial cells and neighboring adipocytes. Here, we investigated the effects of ccRCC on naïve human adipose tissue (hRAN). Human retroperitoneal adipose tissue fragments from two distinct donors (n = 2) were incubated with conditioned media (CMs) derived from ccRCC tumors (T-CM) or renal epithelial cells (Tc-CM). We analyzed the expression of adipocytokines, differentiation and browning markers, metabolic parameters, and steroid hormone receptor profiles. The exposure of hRAN to T-CM or Tc-CM led to significant alterations in the expression of adiponectin and leptin, as well as markers associated with differentiation and browning, including PLIN1, HSL, PGC1α, PPARγ, and UCP1. Adipocytes from treated hRAN were smaller than those from controls, suggesting dedifferentiation. Moreover, expression of FABP4 and MCT1 was significantly increased in explants treated with T-CM compared to control media. Conditioned media from these treated hRAN samples showed elevated lactate secretion, indicating enhanced lactatogenesis. Given the role of sex hormones in metabolic regulation, we examined the expression of estrogen (ER), androgen (AR), and progesterone (PR) receptors. While AR and PR levels remained unchanged, both ERα and ERβ were significantly upregulated after T-CM treatment. Metabolic reprogramming in renal tumors induces profound adaptive changes in adjacent adipose tissue. The dedifferentiation and browning of adipocytes, altered adipocytokine expression, and increased lactate production observed in hRAN reflect the metabolic stress imposed by the tumor environment. Here, we provide evidence, using an ex vivo model, of a dynamic partnership between human adipose tissue and ccRCC tumors. Full article

Cisplatin is an effective chemotherapeutic agent, yet its clinical utility is limited by dose-dependent nephrotoxicity. Alpha-1 antitrypsin (AAT) has cytoprotective, anti-inflammatory, and antiapoptotic properties, but its therapeutic potential in cisplatin-induced acute kidney injury (AKI) remains unclear. A murine cisplatin–AKI model was used to evaluate whether AAT (80 mg/kg) ameliorates renal injury. Renal function, oxidative stress, NADPH oxidase (NOX) isoforms, mitochondrial metabolism, inflammatory mediators, apoptosis, and fibrosis-related markers were assessed using biochemical, histological, immunohistochemical, and Western blot analyses. Cisplatin markedly impaired renal function and induced tubular injury; meanwhile, AAT significantly reversed these changes. Cisplatin also induced severe oxidative stress and disrupted the balance of NOX isoforms; AAT restored redox homeostasis. Cisplatin upregulated CPT1A/PDK4 and suppressed CPT2, UCP3, PGC1α, and DRP1, inducing maladaptive mitochondrial changes, indicating impaired β-oxidation and defective mitochondrial dynamics; AAT reversed these alterations, restoring normal mitochondrial metabolism. IL-1β, IL-6R, OPN, and F4/80 expression, recovery of the Bax/Bcl-2 ratio, and MAPK activation were reduced, indicating decreased inflammation and apoptosis; profibrotic markers were also reduced. AAT confers multifaceted protection against cisplatin-induced AKI by restoring redox balance, mitochondrial homeostasis, and inflammatory and apoptotic signaling. These findings support AAT as a promising therapeutic agent for preventing cisplatin nephrotoxicity. Full article

Brown adipose tissue (BAT) plays a key role in non-shivering thermogenesis and is a promising target for enhancing energy expenditure to combat obesity. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme that catalyzes the conversion of epoxy fatty acids into less active diols. We have reported that local administration of the sEH inhibitor, t-TUCB, to the endogenous interscapular BAT (iBAT) of diet-induced obese mice decreased serum triglycerides and enhanced the expression of essential genes associated with lipid metabolism. Here, the effects of sEH inhibition by t-AUCB were assessed on human brown adipocyte (HuBr) differentiation and in nude mice transplanted with t-AUCB-treated HuBr. HuBr cells were differentiated with t-AUCB (1–10 µM) or the vehicle (0.1% DMSO). HuBr differentiated with t-AUCB at 5 μM (AUCB 5) or DMSO was mixed with matrix gel and transplanted into the nude mice. The mice were then fed a high-fat diet for eight weeks. The mice receiving AUCB 5-treated HuBr exhibited markedly reduced lipid accumulation in the iBAT compared with DMSO or matrix-only controls, along with increased protein expression of thermogenic PGC1α and UCP1, fatty acid transporter CD36, and CPT1A in the iBAT, while the NFκB inflammatory pathways were suppressed in both the AUCB 5 and DMSO groups. Moreover, the PGC1α and CPT1A protein levels were elevated, and the adipocyte sizes were decreased in the epididymal white adipose tissue of the AUCB 5 group. Our findings indicate that the transplantation of HuBr treated with AUCB 5 may stimulate thermogenesis, enhance lipid metabolism, and reduce inflammation in iBAT. Full article

We propose and develop a unified framework for Weyl-type symmetry in von Neumann algebras. Motivated by recent automorphism-rigidity phenomena that identify finite Weyl groups inside automorphism groups of crossed products arising from lattice actions on homogeneous spaces, we introduce the Weyl group of an inclusion $W(M;B):={\mathrm{Aut}}_B\left(M\right)/{\mathrm{Inn}}_B\left(M\right)$, for a unital inclusion $B\subset M$ of von Neumann algebras, and investigate its structure across several rigidity regimes. Our main results (1) prove finiteness or triviality of $W(M;B)$ for large classes of nonamenable crossed products, including hyperbolic and product-type actions with spectral gap and malleability; (2) establish a subgroup-normalizer rigidity principle for inclusions $L(\Lambda )\subset L(\Gamma )$ that identifies ${\mathrm{Aut}}_{L(\Lambda )}\left(L(\Gamma )\right)$ with a discrete group controlled by $N_{\Gamma }(\Lambda )$; (3) show that permutation-type symmetry for product/tensor decompositions is the only possible nontrivial symmetry of the underlying group subalgebras; and (4) extend the analysis to type III factors via Maharam extensions and unique-Cartan phenomena, proving that $W(M;B)$ is discrete and often trivial, leaving only modular flows as outer symmetries. Consequences include new computations of outer automorphism groups, constraints on intermediate subalgebras, and classification consequences for crossed products and amalgamated free products. The methods combine Popa’s intertwining-by-bimodules, spectral-gap and s-malleable deformations, boundary/ucp-map rigidity, and groupoid/Cartan techniques. Full article

Background/Objectives: Cerebral palsy (CP) is the most common cause of physical disability in childhood. While gait improvements are often observed during childhood, it remains unclear whether these gains are sustained into adulthood. This study aimed to evaluate the long-term evolution of gait outcomes from childhood to adulthood in individuals with CP who received orthopedic care early in life. Methods: This retrospective study included 83 adults with cerebral palsy (44 unilateral/uCP, 39 bilateral/bCP; GMFCS I–III) who underwent clinical gait analysis in childhood and again as adults (minimum 4 years between visits, n = 249 CGA). Gait was assessed using the modified Gait Profile Score (mGPS) and normalized walking speed (NWS). The effects of life stage (childhood, adolescence, early adulthood, and adulthood) were analyzed using Kruskal–Wallis tests with post hoc comparisons. Individual clinical transitions were quantified from early adulthood to adulthood, with a minimal clinically important difference (MCID) change in mGPS (1.6°) and NWS (0.20 s⁻¹) for improvement or decline. Results: Longitudinal analysis revealed that while group-average mGPS improved from childhood to adulthood, NWS declined significantly for all patients (p < 0.01). However, individual trajectories from early adulthood to adulthood diverged by CP type. Those with bCP GMFCS II and III had a more frequent clinical decline in mGPS (4/14, 29%), with minimal potential for improvement (1/14, 17%). In contrast, individuals with uCP had less frequent decline (1/17, 6%) and a greater improvement (3/17, 18%). Conclusions: While significant improvements in gait quality are achieved by early adulthood, substantial clinical decline occurs during adulthood in bCP (GMFCS II–III) patients. These findings highlight the need for lifelong monitoring, with re-evaluation regarding the need for surgical interventions from early adulthood to adulthood in bCP patients with greater motor impairments. Full article

Tannins are known for their ability to modify digestion and reduce CH₄ emissions in ruminants. Novel forages able to tolerate water deficits often contain low-to-moderate levels of dietary tannins. The aim of the study was to compare the effect of tannic acid (hydrolysable tannin, HT) and Tannivin (quebracho, condensed tannins, CTs) added to a total mixed ration at a concentration of 2.5% on rumen fermentation over time using in vitro methods. The substrates were incubated with buffered rumen fluid at 39 °C for 0, 3, 6, 12, 24, and 48 h to study dry matter (DM) degradability, tannin disappearance, utilizable protein (uCP), and rumen fermentation parameters. In parallel, gas production was measured using the ANKOM-RF Gas Production System. Gas composition was determined after 24 and 48 h of incubation. DM degradability was influenced by the incubation time (p < 0.001), reaching approximately 50% after 48 h, with a similar course of degradability for both tannin types. Tannin disappearance was significantly influenced by the type of tannins and the incubation time (both p < 0.001), reaching 50% in HTs and 39% in CTs within the first 6 h of fermentation. Production of individual and total VFA and uCP increased during incubation (p < 0.001) but were not influenced by the tannin type. However, the formation of uCP was relatively stable over time. Ammonia-N production increased during the first 12 h of fermentation with both tannin types and the increase continued with HTs (p < 0.001). Gas and methane production increased during fermentation and the increase was more substantial in HTs (p < 0.001). Our results suggest that at moderate concentrations, tannins mainly affect protein metabolism, with a minor effect on rumen fermentation. Full article

We present a simplified phenomenological computational framework that integrates the GABA shunt into established metabolic mechanisms underlying pancreatic beta cell insulin secretion. The GABA shunt introduces carbon into the tricarboxylic acid (TCA) cycle via succinate, thereby functioning as an anaplerotic pathway. This anaplerotic input is coupled to oscillatory cataplerotic fluxes, primarily involving α-ketoglutarate, whose effective extrusion requires coordinated counter-fluxes of malate and aspartate. Within the model, these cataplerotic exchanges are facilitated by UCP2-mediated transport processes and necessitate complementary anaplerotic replenishment through pyruvate carboxylase (PC). Based on this functional interdependence, we introduce the Dual Anaplerotic Model (DAM), which conceptually links two anaplerotic routes—the GABA shunt-mediated pathway and the glucose-dependent PC pathway—into a unified metabolic response module. DAM describes a coordinated, breathing-like redistribution of carbon between mitochondrial and cytosolic metabolite pools, while efficient oxidative metabolism of glucose-derived carbon entering the TCA cycle via pyruvate dehydrogenase is maintained. The model is driven by experimentally observed ATP/ADP and Ca²⁺ dynamics and is not intended to generate autonomous oscillations. Instead, it enables qualitative, phase-dependent visualization of how dual anaplerotic fluxes constrain and shape oscillatory metabolic states in beta cells. DAM provides an integrative conceptual scaffold for interpreting experimental observations and for motivating future quantitative modeling and experimental studies addressing metabolic regulation in physiological and pathophysiological contexts. Full article

Gut microbiota has emerged as a modulator of host metabolism and energy balance. However, the precise microbial metabolites mediating thermogenic activation in obesity remain largely undefined. We investigated the effect of antibiotic treatment under a high-fat diet on metabolites and its contribution to lipolysis and thermogenesis. Antibiotic treatment in high-fat diet-fed rats reduced adiposity and enhanced adaptive thermogenesis. Metabolomics revealed elevated taurine levels in the cecum content and plasma of antibiotic-treated animals, correlating with increased expressions of UCP1 and TGR5 in brown adipose tissue. Taurine enhanced lipolysis and oxygen consumption in mouse adipose tissue and human adipocytes. Thereby, taurine modulated lipolysis dependent on TGR5 signaling in adipose tissue. Human data confirmed that taurine promotes browning of white adipocytes and that acute cold exposure leads to a marked drop in circulating taurine, suggesting its rapid recruitment into thermogenic tissues. Besides its synthesis in the liver and dietary uptake, taurine can be a microbiota-derived metabolite that activates adipose thermogenesis and lipolysis through TGR5 and possibly taurine transporter-dependent mechanisms. These findings uncover a gut–adipose axis with therapeutic potential for metabolic disease. Full article