Search Results (215)

Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial condition associated with significant systemic complications such as cardiovascular disease (CVD), metabolic disorders, muscle wasting, and sarcopenia. While Body Mass Index (BMI) is a well-established indicator of obesity and has prognostic value in COPD, its role in predicting disease outcomes is complex. Muscle wasting is prevalent in COPD patients and exacerbates disease severity, contributing to poor physical performance, reduced quality of life, and increased mortality. Additionally, COPD is linked to metabolic disorders, such as dyslipidemia and diabetes, which contribute to systemic inflammation and worse prognosis and, therefore, should be treated. The systemic inflammatory response plays a central role in the development of sarcopenia. In this review, we highlight the mixed efficacy of statins in managing dyslipidemia in COPD, considering side effects, including muscle toxicity in such a frail population. Alternative lipid-lowering therapies and nutraceuticals, in addition to standard treatment, have the potential to target hypercholesterolemia, which is a coexisting condition present in more than 50% of all COPD patients, without worsening muscle wasting. The interference between adipose tissue and lung, and particularly the potential protective role of adiponectin, an adipocytokine with anti-inflammatory properties, is also reviewed. Respiratory, metabolic and muscular health in COPD is comprehensively assessed. Identifying and managing dyslipidemia and paying attention to other relevant COPD comorbidities, such as sarcopenia and muscle wasting, is important to improve the quality of life and to reduce the clinical burden of COPD patients. Future research should focus on understanding the relationships between these intimate mechanisms to facilitate specific treatment for systemic involvement of COPD. Full article

Childhood obesity is a substantial health problem worldwide. The origin of obesity (increased adiposity) can be partly traced back to intrauterine life. However, the determinants of fetal fat deposition remain unclear. This study investigated the association between cord blood adipocytokines related to lipid metabolism (leptin, adiponectin, and insulin-like growth factor-1 [IGF-1]) and fetal adiposity during gestation. A prospective study was conducted in a cohort of 94 singleton pregnancies. Fetal ultrasonography was performed at 24, 30, and 36 weeks of gestation. Estimated fetal adiposity (EFA) was calculated by integrating measurements of cross-sectional arm and thigh fat area percentages and anterior abdominal wall thickness. Plasma cytokine levels and C-peptide immunoreactivity (as a proxy for fetal insulin resistance) were evaluated in cord blood samples obtained at delivery. The associations of cord blood leptin, adiponectin and IGF-1 levels with EFA at 24, 30, and 36 weeks were determined by multiple linear regression, adjusted for potential covariates. The multivariate analyses indicated that leptin was significantly correlated with EFA at 30 and 36 weeks. Leptin was also positively correlated with C-peptide immunoreactivity in the umbilical cord. Cord adiponectin levels were not associated with EFA across gestation. Cord IGF-1 levels were significantly correlated with EFA and estimated fetal body weight (EFW) at 36 weeks. In conclusion, cord leptin was associated with EFA at 30 and 36 weeks, and IGF-1 was associated with EFA at 36 and EFW at 36 weeks. In Conclusion, cord leptin was associated with EFA at 30 and 36 weeks, and IGF-1 was associated with EFA and EFW at 36 weeks. Considering the effects of leptin and IGF-1 on fetal insulin resistance and lipid metabolism, increased levels of leptin and IGF-1 are potential plasma biomarkers of increased fetal adiposity, which may predispose to infant obesity and metabolic dysfunction in later life. Full article

Background/Objectives: This study aimed to evaluate adipose tissue dysfunction, assessed through adipocytokines and proinflammatory cytokines, in relation to hepatic steatosis (HS) in patients with newly diagnosed type 2 diabetes (T2D). Methods: An observational study evaluated 155 consecutive patients with new-onset T2D; 118 (76.1%) were found to have HS, while the remaining 37 served as the control group without steatosis. Anthropometric status and body mass index (BMI) were evaluated. The biochemical assessment encompassed the measurements of fasting serum lipids, fasting plasma glucose (FPG), liver function tests, adiponectin, leptin, resistin, tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Insulin resistance (IR) was determined using the homeostasis model assessment (HOMA). HS was evaluated using ultrasonographic criteria. Quantitative evaluation of HS was performed by calculating the hepatic steatosis index (HSI). Results: There were statistically significant differences between the groups for age, BMI, weight, waist circumference (WC) and hip circumference, HSI, glucose profile (fasting plasma glucose (FPG), HOMA-IR), liver function tests, adiponectin, leptin, resistin, TNF-α, and IL-6. In multivariate logistic regression analysis, age, smoking, BMI, WC, HOMA-IR, and hypoadiponectinemia were the only independent factors associated with HS. Conclusions: The adipose tissue dysfunction assessed through adipocytokines and proinflammatory cytokines is part of the associated disorders in HS and new-onset T2D. In patients with newly diagnosed T2D, age, smoking, and hypoadiponectinemia consistently emerged as independent predictors of hepatic steatosis. More prospective trials are needed to clarify the “the temporal onset” of adipose tissue dysfunction. Full article

Background: Gastric cancer is a leading cause of cancer-related mortality worldwide, with approximately one million new cases diagnosed annually. While Helicobacter pylori infection remains a primary etiological factor, mounting evidence implicates obesity and lipid metabolic dysregulation, particularly in hypercholesterolemia, as emerging drivers of gastric tumorigenesis. This study investigates the molecular intersections between gastric cancer, obesity, and hypercholesterolemia through a comprehensive multi-omics and systems biology approach. Methods: We conducted integrative transcriptomic analysis of gastric adenocarcinoma using The Cancer Genome Atlas (TCGA) RNA-sequencing dataset (n = 623, 8863 genes), matched with standardized clinical metadata (n = 413). Differential gene expression between survival groups was assessed using Welch’s t-test with Benjamini–Hochberg correction (FDR < 0.05, |log₂FC| ≥ 1). High-confidence gene sets for obesity (n = 128) and hypercholesterolemia (n = 97) were curated from the OMIM, STRING (confidence ≥ 0.7), and KEGG databases using hierarchical evidence-based prioritization. Overlapping gene signatures were identified, followed by pathway enrichment via Enrichr (KEGG 2021 Human) and protein–protein interaction (PPI) analysis using STRING v11.5 and Cytoscape v3.9.0. CD36’s prognostic value was evaluated via Kaplan–Meier and log-rank testing alongside clinicopathological correlations. Results: We identified 36 genes shared between obesity and gastric cancer, and 31 genes shared between hypercholesterolemia and gastric cancer. CD36 emerged as the only gene intersecting all three conditions, marking it as a unique molecular integrator. Enrichment analyses implicated dysregulated fatty acid uptake, adipocytokine signaling, cholesterol metabolism, and NF-κB-mediated inflammation as key pathways. Elevated CD36 expression was significantly correlated with higher tumor stage (p = 0.016), reduced overall survival (p = 0.001), and race-specific expression differences (p = 0.007). No sex-based differences in CD36 expression or survival were observed. Conclusions: CD36 is a central metabolic–oncogenic node linking obesity, hypercholesterolemia, and gastric cancer. It functions as both a mechanistic driver of tumor progression and a clinically actionable biomarker, particularly in metabolically comorbid patients. These findings provide a rationale for targeting CD36-driven pathways as part of a precision oncology strategy and highlight the need to incorporate metabolic profiling into gastric cancer risk assessment and treatment paradigms. Full article

Background: Adipokines secreted by the adipose tissue and placenta play a critical role in regulating metabolic functions that are essential for fetoplacental development and embryonic growth. While adipokines are known to impact a wide range of physiological and pathological conditions, their role in affective disorders during pregnancy remains underexplored. In this study, we aimed to assess the serum levels of distinct adipokines and examine their association with anxiety and comorbid depression in pregnant women. Methods: Third-trimester pregnant women with severe anxiety (ANX, n = 45) and anxiety plus depressive symptoms (ANX + DEP, n = 61) were enrolled in the study, along with healthy control subjects (CTRL, n = 33). Participants were classified using the Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS). Serum levels of adiponectin, adipsin, leptin, and resistin were quantified by flow cytometry-based immunoassay. Clinical, biochemical, and demographic parameters were analyzed using ANOVA with a post hoc Tukey test. Pearson bivariate and partial correlations were performed to assess associations between variables. Results: Adipokine serum levels were significantly higher in the symptomatic groups (ANX, ANX + DEP) than in the CTRL group (p < 0.001). Adiponectin, leptin, and resistin levels positively correlated with anxiety symptoms (HARS, p < 0.01). Furthermore, resistin levels showed a strong association with depressive symptoms (HDRS, p = 0.001) in the ANX + DEP group, after adjusting all parameters by clinical confounders. Conclusions: Our findings revealed that both pro- and anti-inflammatory adipokine levels are elevated in women with affective symptoms during late pregnancy. Pro-inflammatory properties of leptin and resistin may contribute to the severity of anxiety symptoms. Notably, resistin emerges as a key adipokine associated with the expression of depressive symptoms. In addition, adiponectin, acting as an anti-inflammatory mediator, may counteract the inflammatory responses induced by leptin and resistin. These results provide new insights into the role of specific adipocytokine in women with affective disorders during late pregnancy. Full article

Geese (Anser cygnoides) are popular worldwide with consumers for their unique meat quality, egg production, foie gras, and goose down; however, the key genes that influence geese growth remain elusive. To explore the mechanism of geese growth, a total of 500 Zhedong White geese were raised; four high-weight (HW) and four low-weight (LW) male geese were selected to collect carcass traits and for further transcriptomic and metabolomic analysis. The body weight and average daily gain of HW geese were significantly higher than those of the LW geese (p-value < 0.05), and the yields of the liver, gizzard, glandular stomach, and pancreas showed no significant difference between the HW and the LW group (p-value > 0.05). Compared with the LW geese, 19 differentially expressed genes (DEGs) (i.e., COL11A2, COL22A1, and TF) were detected in the breast muscle from the HW geese, which were involved in the PPAR signaling pathway, adipocytokine signaling pathway, fatty acid biosynthesis, and ferroptosis. A total of 59 differential accumulation metabolites (DAMs), which influence the pathways of glutathione metabolism and vitamin B6 metabolism, were detected in the breast muscle between the HW and LW geese. In the liver, 106 DEGs (i.e., THSD4, CREB3L3, and CNST) and 202 DAMs were found in the livers of the HW and LW groups, respectively. DEGs regulated the pathways of the TGF-beta signaling pathway, pyruvate metabolism, and adipocytokine signaling pathway; DAMs were involved in pyrimidine metabolism, nitrogen metabolism, and phenylalanine metabolism. Correlation analysis between the top DEGs and DAMs revealed that in the breast muscle, the expression levels of COL11A2 and COL22A1 were positively correlated with the content of S-(2-Hydroxy-3-buten-1-yl)glutathione. In the liver, the expression of THSD4 was positively correlated with the content of 2-Hydroxyhexadecanoic acid. In addition, one DEG (LOC106049048) and four DAMs (mogrol, brassidic acid, flabelline, and L-Leucyl-L-alanine) were shared in the breast muscle and liver. These important results contribute to improving the knowledge of goose growth and exploring the effective molecular markers that could be adopted for Zhedong White goose breeding. Full article

Traditional Chinese medicine has long acknowledged the therapeutic potential of Tetradium ruticarpum (A.Juss.) T.G.Hartley together with Coptis chinensis Franch in managing metabolic disorders. However, their combined anti-obesity effects and the underlying mechanisms remain poorly characterized. This study investigates the synergistic anti-obesity effects and mechanisms of a combined berberine and evodiamine treatment (BBE) in high-fat diet (HFD)-induced C57BL/6J mice and 3T3-L1 cells. In vitro, cell viability was evaluated using the Cell Counting Kit-8 (CCK-8), while lipid accumulation was assessed through Oil Red O staining and triglyceride content determination. Molecular docking simulations performed with AutoDockTools 1.5.6 software Vina predicted interactions between BBE and key proteins. The analysis of genes and proteins involved in browning and thermogenesis was conducted using quantitative reverse transcription polymerase chain reaction and Western blotting. In vivo, HFD-induced mice were assessed for serum lipids profiles, glucose, insulin, adipocytokines, fat tissue morphology (Hematoxylin and eosin staining), mitochondrial activity (flow cytometry), and protein expression (immunofluorescence). Molecular docking analysis revealed strong binding affinities between BBE and key target proteins, including UCP1, PGC-1α, PRDM16, CIDEA, FGF21, and FGFR1c. BBE significantly reduced lipid accumulation in 3T3-L1 cells, upregulated the mRNA expression of Prdm16, Cidea, Ucp1, and Dio2, elevated UCP1 and PGC-1α protein levels, and activated the FGF21/PGC-1α signaling pathway. In HFD-induced mice, BBE administration led to reduced body weight, smaller adipocyte size, increased adipocyte number, and alleviated hepatic steatosis. Furthermore, it lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and levels of triglycerides (TG), while simultaneously increasing concentrations of high-density lipoprotein cholesterol (HDL-C). BBE also improved glucose tolerance, reduced fasting insulin levels, and modulated adipocytokine levels (reduced leptin, increased adiponectin), while promoting browning gene and protein expression. Overall, the combination of berberine and evodiamine mitigates obesity by enhancing browning and activating the FGF21/PGC-1α signaling pathway. Full article

Kidney transplantation is the preferred treatment for chronic kidney disease, significantly improving patient survival and quality of life. After the procedure, there is a gradual tendency to normalize most of the physiological and metabolic processes, but the need for immunosuppression may lead to new disorders related to the drugs’ side effects and changes in proportions of body composition. The aim of the study was to analyze the concentrations of adipocytokines such as leptin, adiponectin, visfatin, and resistin, and to assess the body composition in patients with stabilized kidney graft function treated with tacrolimus, mycophenolate mofetil, and glucocorticosteroids. A total of 47 participants were enrolled, including 25 kidney transplant recipients on uniform immunosuppressive therapy and 22 healthy controls. The concentrations of leptin, adiponectin, and IL-6 in kidney transplant recipients was significantly higher than in the control group (p = 0.014, p = 0.031, p = 0.000, respectively), while the other adipocytokines, such as visfatin and resistin, do not obtain statistically significant differences. The bioelectrical impedance analysis showed statistically significant differences for fat-free mass index (p = 0.027), visceral fat area (p = 0.023), waist circumference (p = 0.006), fat mass (p = 0.028), and fat mass index (p = 0.034), all of which had higher mean values in the study group. Preliminary findings suggest that kidney transplantation leads to significant alterations in adipocytokines levels, with potential implications for metabolic health. Full article

(1) Background: Overconsumption of processed meats, fats, and carbohydrates drives the obesity epidemic in the USA. Associated with this epidemic are increases in metabolic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. In this study, protein levels of adipocytokines isolated from visceral fat in mice fed high-fat diets with proteins modified through ammonium supplementation were analyzed to determine changes that occur as a result of dietary protein source and its modification based on age or sex. (2) Methods: Male and female C3H/HeJ mice were randomized into six customized diets—Group 1: CCN = Control Chow (CC) + Ammonium Hydroxide Enhancement (AHE); Group 2: CC = Control Chow; Group 3: HFBN = High Fat (HF) AHE Dietary Beef; Group 4: HFB = HF Beef; Group 5: HFCN = HF AHE Dietary Casein; Group 6: HFC = HF Dietary Casein. Mice were censored at six-month intervals, and visceral fat was collected for analysis. This study highlights sex- and age-related changes in cellular adipocytokine protein expression from 12 to 18 months. (3) Results: When compared to dietary casein, dietary-beef-fed mice showed increased expression of adiponectin, leptin, and MCP-1. In dietary casein protein diets, high fat content was correlated with the expression of pro-inflammatory adipocytokines leptin, MCP-1, resistin, VEGF-A, and TIMP-1. Sex-related differences were observed in adiponectin, leptin, and MCP-1 expression levels. AHE of dietary protein decreased the expression of adiponectin, leptin, MCP-1, and TIMP-1. Age-related changes in expression were observed in leptin, MCP-1, and VEGF-A. (4) Conclusions: Our results indicate that the source of dietary protein plays a critical role in determining adipocytokine expression in WAT. Furthermore, this study shows that in addition to dietary protein type (beef or casein), AHE and fat content also impact the relative expression of both pro-inflammatory and anti-inflammatory adipocytokines based on sex over time, with leptin and MCP-1 identified as the most frequently affected. Full article

Cytokines are crucial in various physiological and pathological processes, especially in inflammatory diseases in mammals. However, the comprehensive identification of cytokines and their potential regulatory functions in the mammary glands of Holstein cows suffering from clinical mastitis (CM) remains only partially understood. This study aimed to systematically identify biological processes (BPs) and differentially expressed proteins (DEPs) associated with cytokines and to explore their functions through the analysis of previously obtained data from data-independent acquisition (DIA) proteomics. We confirmed that the dynamic balance between pro- and anti-inflammatory factors is closely associated with dairy mastitis. A total of 4 BPs, comprising 75 upregulated and 16 downregulated DEPs, were identified, particularly in relation to adiponectin (ADIPOQ), which strongly interacts with the other DEPs and participates in peroxisome proliferator-activated receptor (PPAR) and adipocytokine signaling pathways. Immunohistochemical and immunofluorescence staining revealed that ADIPOQ was predominantly localized in the cytoplasm of mammary epithelial cells. Moreover, the expression levels of ADIPOQ mRNA and protein in the mammary glands of the CM group were notably reduced compared to those in the healthy group. A potential mechanism of action of ADIPOQ was suggested, with findings indicating that a decrease in ADIPOQ expression could potentially worsen inflammation in CM. These results offer novel insights into cytokines and the regulatory mechanisms of ADIPOQ in Holstein cows with CM which may benefit the prevention and treatment of dairy mastitis. Full article

Background/Objectives: An increase in body fat is linked to abnormalities in energy metabolism. We aimed at determining cardiometabolic risk in Algerian participants with obesity alone and with or without type 2 diabetes. The study measured the concentrations of circulating adipocytokines (leptin, adiponectin, resistin), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) to identify and examine how imbalances in adipocytokines may affect the parameters of cardiometabolic health. Methods: Algerian participants (n = 300) were recruited and divided into three groups: control, obese, and type 2 diabetics (with two sub-groups: with and without obesity). Insulin resistance was evaluated using HOMA-IR, while ELISA was used to measure adipocytokines. Atherogenic index in plasma (AIP), adiponectin-leptin ratio (ALR), and visceral adiposity index (VAI) were also assessed. One-way ANOVA was used to compare obesity and diabetes groups to the control one (p < 0.05). Logistic regression analysis was conducted to strengthen the robustness of statistical correlations. Results: Participants with reduced adiponectin-leptin ratio (ALR) and elevated levels of resistin, TNF-α, and IL-6 are found to be at higher risk of cardiovascular diseases. An imbalance in adipocytokine levels is caused by a decrease in adiponectin concentrations, and an increase in pro-inflammatory adipocytokines that maintain and exacerbate energy imbalance and induces hyperinsulinemia, exposing individuals to a high risk of cardiovascular diseases. Conclusions: Given that ALR is a functional biomarker of inflammation, insulin resistance, and adipose tissue dysfunction, targeting ALR could potentially be a therapeutic approach to coping with obesity-related cardiometabolic risks. Mediterranean diet, weight loss, and increased physical activity can be key components to promote healthy adipose tissue through the increase in ALR. Full article

Background: Subcutaneous fat deposition is associated with ducks’ meat quality and the methods used to cook them. However, the reasons underlying the differences in the lipid deposition of small-sized Wuqin10 meat ducks remain unclear. Method: In the present study, to elucidate the metabolic mechanisms of lipid deposition, we comprehensively analyzed the transcriptomics and lipidomics of subcutaneous fat in Wuqin10 meat ducks with different subcutaneous thicknesses with six replicates. Results: A total of 1120 lipids were detected in the lipidomic analysis, and 39 lipids were inexorably regulated in the ducks with the thick subcutaneous layer compared to those with the thin layer; further, the up-regulated lipids were primarily triglycerides (TGs), which may have resulted in adipocyte enlargement. Furthermore, the transcriptomic analysis identified 265 differentially expressed genes (DEGs), including 119 down-regulated and 146 up-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were significantly enriched in the histidine, arginine, proline metabolism signaling and adipocytokine signaling pathways. The protein–protein interaction (PPI) network in Cytoscape 3.8.2 identified hub genes HSP90AA1, RUNX2, ACTN2, ACTA1, IL10, CXCR4, EGF, SOCS3 and PTK2, which were associated with the JAK-STAT signaling pathway and regulation of adipocyte hypertrophy. Conclusion: Taken together, our findings reveal the patterns of lipids and the gene expression of subcutaneous fat, providing a basis for future studies of subcutaneous fat deposition in small-sized meat ducks. Full article

In obesity, recent research revealed that increased expression of the growth hormone secretagogue receptor (GHSR) in macrophages plays a pivotal role in the development of meta-inflammation, promoting macrophage infiltration and pro-inflammatory polarization. This study aimed to examine the association between GHSR-1a expression in atherosclerotic plaques and adjacent perivascular adipose tissue (PVAT) from 11 patients with obesity and peripheral artery disease (PAD) who underwent revascularization procedures. Immunohistochemistry was used to assess the expression of CD68, CD80, and CD14, while tissue homogenate levels of adiponectin, leptin, IL-6, and CRP were quantified via ELISA. Serum markers of inflammation were also measured. Among patients with GHSR-1a-positive (+) macrophages in atherosclerotic plaques, we observed significantly higher white blood cell counts and platelet-to-lymphocyte ratios in serum, a lower adiponectin-to-leptin ratio, and elevated IL-6 levels in both arterial and PVAT homogenates. Our findings suggest a link between GHSR-1a and macrophage/monocyte infiltration, macrophage polarization, and adipocytokine secretion in atherosclerotic plaques associated with obesity-induced PVAT dysfunction. Full article

Background: Obesity impairs renal function through direct mechanisms, such as proinflammatory adipocytokine production, and indirect mechanisms, including obesity-related comorbidities. Despite the increasing prevalence of obesity and chronic kidney disease (CKD), clinical guidelines for their combined management remain lacking. Very Low Energy Ketogenic Therapy (VLEKT) has demonstrated efficacy in weight loss, but evidence on its safety and efficacy in individuals with obesity and mild renal impairment is limited. This study aimed to assess the efficacy and safety of Phase 1 of VLEKT in individuals with obesity and mild renal impairment. Methods: This cross-sectional study included 73 individuals with overweight or obesity (mean age 53.7 ± 8.8 years; BMI 35.3 ± 4.2 kg/m²) and an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m² (evaluated using the CKD-EPI equation). Anthropometric (weight, BMI, and waist circumference) and biochemical parameters (fasting plasma glucose, insulin, cholesterol profile, triglycerides, AST, ALT, and urea) were collected at baseline and after 45 (±2) days of Phase 1 of VLEKT. Results: At baseline, 54.8% of participants had an eGFR <90 mL/min/1.73 m², while 45.2% had an eGFR ≥ 90 mL/min/1.73 m², with no significant differences in sex distribution. After 45 (±2) days of Phase 1 of VLEKT, both groups showed significant reductions in BMI (p < 0.001), waist circumference (p < 0.001), fasting plasma glucose (p ≤ 0.004), insulin (p < 0.001), HOMA-IR (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), LDL/HDL ratio (p ≤ 0.002), triglycerides (p ≤ 0.009), AST (p ≤ 0.034), and ALT (p ≤ 0.009). Notably, the eGFR significantly increased in participants with an eGFR < 90 mL/min/1.73 m² (p < 0.001), while no changes were observed in those with an eGFR ≥ 90 mL/min/1.73 m². Conclusions: Phase 1 of VLEKT could effectively promote weight loss and metabolic improvements without compromising renal function, even in individuals with obesity and mild renal impairment. Further research is warranted to confirm the efficacy and safety of VLEKT and to assess outcomes across all protocol phases. Full article

To assess the impact of tannic acid (TA) on the hepatic health of the Chinese soft-shelled turtle, the individuals were fed diets containing 0 (CG), 0.5, 1, 2, and 4 g/kg TA diets for 60 days (0 hps). Afterwards, the turtles were challenged with 15 °C cold stress for 24 h (24 hps) and then recovered to 28 °C for 24 h (48 hps). The results indicated that 4 g/kg TA has a significant toxic effect on the turtles after 60-day administration. The hepatic T-SOD, CAT, GSH-Px, and T-AOC activities in the TA2 were increased at 0 hps and 24 hps (p < 0.05) compared with CG. Similarly, Sod1, Sod2, Cat, Gsh-px3, and Gsh-px4 mRNA levels in the TA2 were higher than in the other four groups at 0 hps and 24 hps (p < 0.05). The histology data showed that 4 g/kg TA induced injuries in liver at 0 hps and after temperature fluctuation, whereas the 2 g/kg TA effectively attenuated the hepatic injuries. A total of 202 differentially expressed metabolites (DEMs) in the CG vs. TA2 and 115 DEMs in the LTCG vs. LTTA2 were separately detected by the metabolome. The cephalosporin C, protoporphyrin, bis(2-ethylhexyl) phthalate, 2-acetamidoethylphosphonat, verbasosid, and norcocain, were obvious DEMs in the CG vs. TA2. Furthermore, valienone 7-phosphate, 5-HETE, pregnanetriolone, 4-keto-anhydrotetracyclin, dephospho-CoA, and lysoPC(18:4(6Z,9Z,12Z,15Z)/0:0) were top DEMs in the LTCG vs. LTTA2. The “adipocytokine signaling pathway” and “AMPK signaling pathway” were the key pathways enriched in the CG vs. TA2, while “fatty acid biosynthesis”, “steroid biosynthesis”, and “linoleic acid metabolism” were most abundant in the LTCG vs. LTTA2. Generally, this research indicated that 2 g/kg TA could protect hepatic health from temperature fluctuations by improving antioxidant capacity, reducing histological injuries, and regulating lipid-related signaling pathways. Full article