Search Results (4,422)

Non-alcoholic fatty liver disease (NAFLD), often associated with obesity, has become a serious public health matter. NAFLD is characterized by an excessive lipid accumulation in hepatocytes, mainly stored as triglycerides. The marine microalga Phaeodactylum tricornutum is well known for its richness of bioactive compounds, particularly lipids. Therefore, different natural lipid extracts from P. tricornutum are deciphered to jugulate or prevent obesity leading to NAFLD. In this study, the main focus was on the effects of purified neutral and polar lipid extracts from P. tricornutum in a cellular model of NAFLD. Human HepG2 cells were used and exposed for 24 h to 250 μM palmitate to induce NAFLD with or without microalgal lipid extracts. Data showed that neutral lipid extract presented lower viability and cytotoxic activities on HepG2 at 75 µg/mL. The impact on apoptosis was around 5% and below the threshold. Nevertheless, the use of neutral lipid at 50 µg/mL induced a decrease in the number and size of lipid droplets, and so, preventing NAFLD. On the contrary, the polar lipid extract had no effect on the accumulation of triglycerides in HepG2 cells. To conclude, neutral lipid extract seemed to be a good candidate to prevent NAFLD. Full article

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants—astaxanthin and Garcinia indica (kokum)—in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders. Full article

Long-term excessive fat intake can easily induce metabolic diseases such as fatty liver and hyperlipidemia. As a natural active ingredient, polysaccharides exhibit notable lipid-lowering effects and can serve as effective lipid regulators. Nevertheless, the lipid-lowering effect of Arabica coffee cherry peel polysaccharides (CCPPs) and the underlying regulatory mechanism remain poorly understood. This study isolated polysaccharides from coffee cherry peel, and their functional properties and the lipid-lowering effects and mechanisms on hyperlipidemic mice. In high-fat diet-fed (HFD-fed) mice, CCPP administration had significant regulatory effects on various metabolic parameters. In laboratory mice where hyperlipidemia is induced by a high-fat diet, CCPP administration improved serum lipid levels and demonstrated anti-inflammatory and antioxidant effects. These benefits were achieved by reducing pro-inflammatory cytokine expression, enhancing antioxidant enzyme activity, and lowering overall oxidative stress. Additionally, it effectively decreased fat area in liver tissues and adipocytes. Specifically, compared with the control group, after high-dose CCPP intervention, the adipocyte area of mice on a high-fat diet was significantly reduced by 41.3%. Notably, CCPP intervention resulted in a shift in the gut microbiota composition. At the phylum level, the model group showed a significant increase in Bacillota and a concomitant reduction in Bacteroidetes in comparison with the control group. Compared with the model group, CCPP intervention, especially in the CCPP-H group, resulted in an increase in the proportion of Bacteroidetes and a decrease in Bacillota. At the genus level, CCPP modulated the abundances of key bacterial genera; for instance, the relative abundance of Lachnospiraceae_NK4A136_group increased from 2.64% in the model group to 11.9% in CCPP-H group, while Faecalibaculum decreased from 62.69% to 41.27% in CCPP-L group and 25.29% in CCPP-H group. These shifts suggest that CCPP has a reparative effect on the gut microbial composition, potentially contributing to the promotion of gut health. Taken together, these factors highlight the promise of CCPP as a functional food ingredient for dietary interventions to ameliorate obesity and hyperlipidemia. Full article

Curcumin, a natural polyphenol derived from turmeric, functions as a potent exogenous antioxidant and exhibits a range of benefits in the prevention and management of metabolic diseases. Despite its extremely low systemic bioavailability, curcumin demonstrates significant bioactivity in vivo, a phenomenon likely attributable to its accumulation in the intestines and subsequent modulation of systemic oxidative stress and inflammation. This article systematically reviews the comprehensive regulatory effects of curcumin on systemic metabolic networks—including glucose metabolism, amino acid metabolism, lipid metabolism, and mitochondrial metabolism—and explores their molecular basis, particularly how curcumin facilitates systemic metabolic improvements by alleviating oxidative stress and interacting with inflammation. Preclinical studies indicate that curcumin accumulates in the intestines, where it remodels the microbiota through prebiotic effects, enhances barrier integrity, and reduces endotoxin influx—all of which are critical drivers of systemic oxidative stress and inflammation. Consequently, curcumin improves insulin resistance, hyperglycemia, and dyslipidemia across multiple organs (liver, muscle, adipose) by activating antioxidant defense systems (e.g., Nrf2), enhancing mitochondrial respiratory function (via PGC-1α/AMPK), and suppressing pro-inflammatory pathways (e.g., NF-κB). Clinical trials have corroborated these effects, demonstrating that curcumin supplementation significantly enhances glycemic control, lipid profiles, adipokine levels, and markers of oxidative stress and inflammation in patients with obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Therefore, curcumin emerges as a promising multi-target therapeutic agent against metabolic diseases through its systemic antioxidant and anti-inflammatory networks. Future research should prioritize addressing its bioavailability limitations and validating its efficacy through large-scale trials to translate this natural antioxidant into a precision medicine strategy for metabolic disorders. Full article

Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed. The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response. Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models. The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC. In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ⁹-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems. Full article

Background: Depression and Metabolic Dysfunction-Associated Steatotic Fatty Liver Disease (MASLD) are common chronic diseases, respectively. However, the causal and molecular links between them remain unclear. In order to explore whether depression contributes to an increased risk of MASLD and whether inflammation mediates this effect, we integrated multi-level evidence from the epidemiology of the National Health and Nutrition Examination Survey (NHANES), the genetics of GWAS, the transcriptomes of GEO, and single-cell RNA sequencing datasets. Methods: A multi-level integrative analysis strategy was used to validate this pathway. First, a cross-sectional epidemiological analysis based on NHANES data was used to reveal the association between depression and MASLD, and to explore the mediating role of inflammation and liver injury markers. Secondly, a two-sample Mendelian randomization analysis was used to infer the causal direction of depression and MASLD, and to verify the mediating effect of systemic inflammation and liver injury indicators at the genetic level. Then, the transcriptome co-expression network analysis and machine learning were used to screen the common hub genes connecting the two diseases. Finally, single-cell transcriptome data were used to characterize the dynamic expression of potential key genes during disease progression at cellular resolution. Results: Depression significantly increased the risk of MASLD, especially in women (OR = 1.39, 95%CI [1.17–1.65]). Parallel mediation analysis showed that high-sensitivity C-reactive protein (hs-CRP) (p < 0.001), γ-glutamyltransferase (GGT) (p < 0.001), and alkaline phosphatase (ALP) (p < 0.001) mediated this relationship. Mendelian randomization analysis confirmed the unidirectional causal effect of depression on MASLD, and there was no reverse association (β = 0.483, SE = 0.146, p = 0.001). Weighted gene co-expression network analysis and machine learning identified CD40LG as a potential molecular bridge between depression-associated immune modules and MASLD. In addition, single-cell data analysis revealed a stage-specific trend of CD40LG expression in CD4⁺ T cells during MASLD progression, while its receptor CD40 was also activated in B cells. In the female sample, CD40LG maintained an upward trend. However, the stability of this result is limited by the limited sample size. Conclusions: This study provides converging multi-omics evidence that depression plays a causal role in MASLD through inflammation-mediated immune signaling. The CD40LG-CD40 axis has emerged as an immune mechanism that transposes depression into the pathogenesis of MASLD, providing a potential target for the intervention of gender-specific metabolic liver disease. Full article

Fatty liver in fish is characterized by excessive lipid accumulation, driven by factors such as inflammation, oxidative stress, and the overexpression of lipid-related genes. This condition can lead to metabolic dysfunction and reduced disease resistance, resulting in growth disorders and even mortality. Increasing incidence of fatty liver is closely linked to environmental conditions and feeding practices, posing significant challenges to the aquaculture industry. This paper offers a comprehensive overview of hepatic steatosis, with a particular emphasis on fish species. Through a detailed review of various scholarly works, this paper seeks to identify common patterns, emerging trends, and measurable correlations, highlighting the critical importance of understanding this complex relationship. The study of fatty liver is conducted across three dimensions: influencing factors, underlying mechanisms, and potential solutions. Currently, numerous factors contribute to the development of fatty liver, such as feed composition and environmental temperature. On a mechanistic level, the research explores lipid accumulation, inflammation, oxidative stress, and related processes. Furthermore, the paper suggests various solutions and preventive strategies, including considering environmental adaptability during animal migration, employing genetic enhancement techniques, modifying feeding practices, investigating the Nrf2 pathway, and utilizing rapamycin. These findings have significant implications for fisheries management and aquaculture practices, providing valuable insights to enhance sustainability in the industry. Full article

Purpose: To investigate associations between lipid oxidation biomarkers (oxylipins), antioxidant micronutrients, lipoprotein particles, and apolipoproteins in multiple sclerosis (MS). Methods: Blood and neurological assessments were collected from 30 healthy controls, 68 relapsing remitting MS subjects, and 37 progressive MS subjects. Hydroxy (H) and hydroperoxy lipid peroxidation products of the polyunsaturated fatty acids (PUFAs) arachidonic (20:4, ω-6), linoleic (octadecadienoic acid or ODE, 18:2, ω-6), eicosapentaenoic (20:5, ω-3), and α-linolenic (18:3, ω-3) acids were measured using liquid chromatography–mass spectrometry. Antioxidant micronutrients, including β-cryptoxanthin and lutein/zeaxanthin, were quantified by high-performance liquid chromatography. Lipoprotein and metabolite profiles were obtained using nuclear magnetic resonance spectroscopy. Regression models were adjusted for age, sex, body mass index, and disease status. Results: The 9-hydroxy octadecadienoic acid to 13-hydroxy octadecadienoic acid ratio (9-HODE/13-HODE ratio), which reflects autoxidative versus enzymatic oxidation, was associated with MS status (p = 0.002) and disability on the Expanded Disability Status Scale (p = 0.004). Lutein/zeaxanthin (p = 0.023) and β-cryptoxanthin (p = 0.028) were negatively associated with the 9-HODE/13-HODE ratio. Apolipoprotein-CII, a marker of liver-X-receptor (LXR) signaling, was associated with 9-HODE/13-HODE ratio and other oxylipins. Octadecadienoic fatty acid-derived oxylipins were negatively associated with LC3A, a mitophagy marker, and positively correlated with 7-ketocholesterol, a cholesterol autoxidation product. Conclusions: Autoxidation of PUFAs is associated with greater disability in MS. Higher β-cryptoxanthin and lutein/zeaxanthin were associated with reduced auto-oxidation. Lipid peroxidation shows associations with LXR signaling, mitophagy, inflammation, and cholesterol autoxidation. Full article

Polyunsaturated fatty acids (PUFAs), particularly omega-3 derivatives such as docosahexaenoic acid (DHA), are precursors of specialized pro-resolving mediators (SPMs) that actively orchestrate the resolution of inflammation. Among these, maresins (MaRs) have gathered increasing attention due to their potent immunomodulatory and tissue-regenerative properties. This review provides a comprehensive synthesis of the current knowledge on the biosynthesis, structural diversity, and biological functions of MaRs, with a focus on MaR1. We discuss the enzymatic pathways involved in the generation of MaR1, MaR2, MaRs conjugates in tissue regeneration (MCTRs), and maresin-like lipid mediators (MaR-Ls), highlighting their roles in modulating inflammatory responses, promoting phagocytosis, and restoring tissue homeostasis. Preclinical evidence from in vitro and in vivo models demonstrates that MaRs exert protective effects in a wide range of pathological contexts, including neuroinflammation, liver injury, cardiovascular dysfunction, pulmonary diseases, and metabolic disorders. Although their therapeutic promise is well-supported, key gaps remain in the understanding of MaRs biosynthesis, receptor specificity, and translational applicability. This review emphasizes the importance of advancing mechanistic and clinical research to fully harness MaRs as part of next-generation therapeutics in inflammation-driven diseases. Full article

Background/Objectives: Sex-specific differences in metabolic dysfunction-associated fatty liver disease (MAFLD)-related hepatocellular carcinoma (HCC) remain poorly understood. This study aimed to clarify sex-associated disparities in disease progression and recovery using a diethylnitrosamine (DEN) plus Western diet/fructose-induced murine model combined with artificial intelligence (AI)-assisted histological analysis. Methods: Male and female C57BL/6J mice received a single diethylnitrosamine injection and were fed a Western diet/fructose regimen for 38 weeks, followed by an 8-week recovery period on standard chow. Serum biochemical parameters were measured, and liver histology was assessed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy. Steatosis and fibrosis were quantified within tumor and adjacent non-tumor regions using AI-based image analysis. Results: Male mice developed more severe disease phenotypes, including greater tumor burden and higher serum alanine aminotransferase levels, compared with females. Following dietary recovery, female mice showed substantial reductions in tumor number and hepatic steatosis, particularly in non-tumor regions; in contrast, male mice demonstrated only minimal improvement. AI-assisted quantification confirmed considerable regression of both steatosis and fibrosis in females and moderate fibrosis improvement in both sexes. Conclusions: These findings indicate sexual dimorphism in the progression and regression of MAFLD-related HCC, with females exhibiting enhanced metabolic and histological recovery. The results underscore the importance of considering sex as a biological variable in preclinical metabolic dysfunction–associated fatty liver disease-related hepatocellular carcinoma research and highlight the value of AI-enhanced imaging for precise, objective evaluation of liver histology. Full article

Background: Metabolically associated fatty liver disease (MASLD) constitutes a major burden. Glucagon-like peptide-1 agonists (GLP-1) could improve hepatic steatosis as well as weight loss. However, the effect of GLP-1 agonists on patients with and without diabetes and the effect of newer drugs (dual and triple agonists) are unclear. Objective: To investigate the effect of GLP-1 agonists, including dual and triple agonists, in patients with metabolic-associated liver steatosis and steatohepatitis, while exploring their effect on patients with and without type 2 diabetes. Methods: We searched PubMed, Scopus, and Web of Science in October 2025 for randomized parallel controlled trials that investigated the effect of GLP-1 agonists in patients with MASLD or metabolic-associated steatohepatitis (MASH). We assessed the quality of the included studies using Cochrane ROB2. We performed the analysis using RevMan 5.4. We performed subgroup analysis based on the status of diabetes, the control group, and the class of GLP-1 agonist (single, dual, or triple). Results: We included twenty studies. Compared to the control group, GLP-1 agonists were associated with a statistically significant increase in the resolution of MASH without worsening fibrosis (RR 3.03, p < 0.0001) and at least one stage of liver fibrosis without the worsening of MASH compared to the control group (RR: 1.45, p < 0.00001). GLP-1 agonists were associated with a statistically significant weight reduction (SMD −1.11, p < 0.0001), glycosylated hemoglobin (SMD −0.81, p < 0.00001), levels of aspartate aminotransferase (SMD −0.48, p = 0.008), and alanine aminotransferase (SMD −0.54, p = 0.008). However, in patients without type 2 diabetes, GLP-1 agonists had no significant effect on weight loss (SMD −0.97, p = 0.12) or improvement in fibrosis (RR 1.54, p = 0.24). There was a statistically significant increase in the overall adverse events (RR 1.10, p < 0.00001), while there was no significant difference in serious adverse events (p = 0.35). Conclusions: GLP-1 agonists improved liver fibrosis, steatohepatitis, weight loss, HbA1c, and liver enzymes in patients with MASLD or MASH. Overall, GLP-1 agonists were associated with a significantly higher risk of adverse events compared to the control, while serious adverse events were comparable between both groups. There was no significant effect on weight loss or improvement in fibrosis in patients without type 2 diabetes. However, there was a limited number of studies in this population. Thus, further research is needed before recommendations can be made for this subgroup. Full article

Bupleuri radix has demonstrated therapeutic potential in treating liver disorders, and polysaccharides are one of its main bioactive components; however, the effects of Bupleuri radix polysaccharides (BRP) on metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. This study aimed to identify the BRP fractions with anti-MASLD activity and elucidate their underlying mechanisms. We prepared BRP and characterized its physicochemical properties. It markedly alleviated liver injury and restored intestinal barrier function in MASLD. The correlation analysis between transcriptomics and targeted metabolomics showed that BRP restored intestinal acetic acid and propionic acid, with acetic acid activating AMPK and propionic acid promoting cholesterol efflux and metabolism in the liver, thereby reducing lipid accumulation in hepatocytes. Mechanistically, 16S RNA sequencing and diversity analysis indicated that BRP enriched short chain fatty acids (SCFAs)-producing bacteria, such as the genus Muribaculaceae, and inhibited pro-inflammatory microbiota. Interestingly, Paramuribaculum intestinale (P. intestinale), a representative species in the genus Muribaculaceae, synergistically enhanced BRP in improving liver and colonic mucosal damage in MASLD. In conclusion, our findings revealed that BRP improved MASLD by regulating Muribaculaceae-derived SCFAs in the gut–liver axis and could be used in combination with probiotics as a novel therapeutic strategy for MASLD. Full article

Background/Objectives: Roux-en-Y gastric bypass (RYGB) improves obesity-related metabolic disorders, yet post-operative dietary composition critically shapes outcomes. This study explored how RYGB and high-fat diet (HFD) differentially regulate hepatic transcriptional programs. Methods: We performed RNA-seq on liver tissues from diet-induced obese C57BL/6 male mice 8 weeks post-RYGB or sham surgery, maintained on chow or HFD. Differentially expressed genes (DEGs) were identified using DESeq2. Gene sets were categorized as RYGB-induced (commonly regulated by surgery across diets), Reversal (RYGB-driven counter-regulation of obesity-induced changes), and HFD-induced (commonly regulated by diet). A subset of RYGB-specific HFD-induced genes was derived by excluding HFD-induced genes from the RYGB Chow vs. RYGB HFD contrast. Pathway enrichment was conducted using STRING. Results: RYGB induced 365 DEGs, including pathways related to extracellular remodeling and reduced mitochondrial/antioxidant activity. Among these, 119 Reversal genes countered obesity-associated transcriptional patterns and accounted for ~27% of the RYGB-induced enrichment results. HFD regulated 860 DEGs, highlighting stress responses and translational repression. Lastly, a set of 426 RYGB-specific HFD-induced genes revealed persistent hepatic inflammation, coagulation, and iron dysregulation under HFD despite surgery. Conclusions: RYGB induces robust hepatic transcriptomic changes that attenuate obesity-driven dysregulation, including a coordinated reprogramming of iron-handling pathways. However, high dietary fat partially overrides these benefits, promoting inflammatory, metabolic stress, and iron-related stress. Optimizing post-operative diets and carefully managing micronutrient intake, especially iron, may enhance RYGB’s metabolic efficacy and long-term liver health. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a highly prevalent hepatic condition closely linked to metabolic syndrome (MetS). Epigenetic regulators such as microRNAs (miRNAs) have emerged as critical modulators of the molecular pathways underlying MASLD pathogenesis, offering new perspectives for non-invasive diagnosis and targeted therapy. This study aimed to identify and characterize target genes and pathways regulated by two key hepatic miRNAs, namely miR-122 and miR-29a, through a comprehensive in silico bioinformatics approach, to better understand their functional roles in MASLD and MetS. Methods: Target genes of miR-122 and miR-29a were predicted using three databases (TargetScan, DIANA-microT-CDS, and miRWalk), and those identified by at least two databases were selected for downstream analyses. Functional enrichment was performed using Gene Ontology and KEGG pathway analysis. Gene networks and biological process maps were constructed using Metascape, clusterProfiler and Cytoscape. Results: miR-122 was found to negatively regulate genes involved in lipid metabolism, insulin signaling, and inflammatory pathways, including PPARGC1A, PPARA, LPL, TLR4, and HMGCR, contributing to insulin resistance and liver dysfunction. By contrast, miR-29a demonstrated potential hepatoprotective effects by targeting LEP, INSR, IL13, and IL18, enhancing insulin sensitivity and reducing fibrogenic activity. Enrichment analysis revealed strong associations with biological processes, such as STAT phosphorylation, lipid homeostasis, and inflammatory signaling, as well as associations with cellular components, including lipoproteins and plasma membranes. miR-122 and miR-29a exhibit opposing regulatory functions in MASLD pathogenesis. Whereas miR-122 is associated with disease progression, miR-29a acts protectively. These miRNAs may serve as promising biomarkers and therapeutic targets in MASLD and related metabolic conditions. Further validation through experimental and clinical studies is warranted. Full article

Obesity and metabolic disorders are an increasing concern in companion animals, creating demand for herb-derived nutraceuticals and functional feeds. This study evaluated whether a water extract of Aster pekinensis (AP) ameliorates high-fat-diet (HFD)-induced obesity and metabolic dysfunction in mice. The phytochemical profile of AP was characterized by mass spectrometry, revealing oleanane-type triterpenoid saponins and dicaffeoylquinic acids. Male C57BL/6 mice were fed an HFD and orally given AP (10–200 mg/kg/day) for 12 weeks, with normal diet and untreated HFD groups as controls. AP at 50–200 mg/kg/day reduced body-weight gain, adipose tissue mass and food efficiency without lowering food intake, and improved fasting glucose and atherogenic lipid indices. AP also enhanced glucose tolerance and insulin sensitivity, attenuated hepatic steatosis, hepatocellular ballooning, lobular inflammation and non-alcoholic fatty liver disease (NAFLD) Activity Score, and decreased serum liver enzyme activities. These effects were accompanied by modulation of hepatic genes involved in lipogenesis and inflammation. Together, these findings indicate that AP extract mitigates diet-induced obesity and NAFLD-like liver injury and supports further development as a herb-derived nutraceutical or functional feed ingredient for managing obesity-related metabolic disorders in companion animals. Full article