Search Results (194)

Background/Objectives: Response to neoadjuvant chemotherapy (NAC) varies substantially among breast cancer patients and is only partially explained by tumor-intrinsic factors. The gut microbiome has emerged as a potential modulator of chemotherapy efficacy, yet its role in breast cancer remains underexplored. This study aimed to characterize gut microbial composition, functional potential, and microbially derived metabolites in breast cancer patients undergoing NAC. Methods: baseline stool samples from 39 chemotherapy-naïve breast cancer patients undergoing NAC were analyzed using shotgun metagenomic sequencing and targeted metabolomics. Patients were stratified by pathological complete response (pCR, n = 17; no pCR, n = 22). Microbial taxonomic and functional profiles, short-chain fatty acids (SCFAs) and bile acids were assessed, with subgroup analysis performed in triple-negative breast cancer (TNBC). Results: Patients achieving pCR exhibited significantly higher baseline microbial richness compared to non-responders (p = 0.040). Differential abundance analysis revealed enrichment of Dialister, Kineothrix, and Jutongia in responders, whereas Rothia, Leuconostoc, Klebsiella, Jingyaoa, Cuneatibacter, Youxingia, and Bittarella were enriched in non-responders. SCFAs (acetate, propionate and butyrate) positively correlated with microbial glucose catabolic pathways, while caproate was negatively associated with multiple amino acid, lipid, vitamin, and cell wall biosynthesis pathways, including peptidoglycan maturation. Metabolomic analysis identified higher deoxycholic acid (DCA) levels in non-responders and increased C6 levels in responders, although these associations did not remain significant after multiple testing correction. Similar trends were observed in the TNBC subgroup (n = 15). Conclusions: Baseline gut microbiome diversity, taxonomic composition, and functional metabolic potential are associated with response to neoadjuvant chemotherapy in breast cancer, supporting the gut microbiome and its produced metabolites as a potential biomarker of treatment efficacy. Full article

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article

Background: Uncontrolled diabetes is characterised by a loss of blood glucose control and increased oxidation of fatty acids to produce ATP. Use of metabolic inhibitors to blunt fatty acid oxidation and restore glucose metabolism is a poorly studied intervention for diabetes. Methods: Steptozotocin-induced diabetes was developed in Wistar male rats. A subset was supplemented with mildronate (100 mg/kg—14 days). Exploiting liquid chromatography-mass spectrometry for workflows including ion exchange-, C18-reverse phase- and HILIC-based chromatography methods, metabolite levels were quantified in plasma liver and brain tissue. Using both untargeted and targeted metabolomic analysis changes to the global tissue metabolome and individual metabolic pathways were estimated. Results: We document that an inhibitor of carnitine synthesis, mildronate, decreased plasma (50% p < 0.01) carnitine abundance and decreased plasma glucose concentration by one-third compared to streptozotocin (STZ)-treated rats (p < 0.001). Targeted metabolomic analysis of the liver showed decreased alpha-ketoglutarate abundance (35% p < 0.05) by STZ diabetes that was further decreased following mildronate treatment (50% p < 0.05). For both beta-hydroxybutyrate and succinate levels, STZ diabetes increased hepatic abundance by 50% (p < 0.05 for both), which was restored to control levels by mildronate (p < 0.05 for both). In contrast, brain TCA intermediate abundances were unaffected by either STZ diabetes or mildronate (NS for all). STZ diabetes also decreased abundance of pentose phosphate pathway (PPP) metabolites in the liver (glucose-6-phosphate, 6-phosphogluconolactone, 6-phosphogluconate 50% for all; p < 0.05), which was not restored by mildronate treatment. However, brain PPP metabolite abundance was unchanged by STZ diabetes or mildronate (NS for all). However, mildronate treatment did not affect the increased abundance of brain sorbitol, sorbitol-6-phosphate and glucose-6-phosphate as a result of STZ diabetes. Conclusions: Together, these observations highlight the potential role that metabolic inhibitors, like mildronate, may play in restoring blood glucose for diabetic patients, without a direct effect of tissues that represent obligate consumers of glucose (e.g., brain) whilst manipulating fat oxidation in tissues such as the liver. Full article

(1) Lifestyle changes to modify unhealthy dietary patterns with the goal of preventing MASLD have proven challenging. Here, dietary proteins and their modification with ammonium hydroxide enhancement (AHE) provide molecular evidence that this novel approach may attenuate the development of MASLD without undue dietary adjustments, potentially bypassing non-compliance. (2) High-fat diets containing dietary beef (HFB) or casein (HFC) + AHE (HFBN and HFCN, respectively) were fed to 256 C3H/HeJ female and male mice long term. At 6, 12, or 18 months, hepatic samples were analyzed with targeted metabolomics (glucose, lactate, alanine, glutamine, carnitine) and Western analysis (β-catenin, glutamine synthetase, CYP3A4). RNA sequencing was performed on samples collected at 18 months (n = 3; male HFC n = 2). (3) Metabolomics results showed that at 18 months, hepatic glutamine was greater in HFBN versus HFCN in females, whereas in males, hepatic glutamine, glucose and lactate were lower in HFBN versus HFCN. Additionally, diets with AHE decreased β-catenin and CYP3A4 protein expression in males. Ingenuity pathway analysis (IPA) of RNA-seq data predicted that HFBN activates PPARα signaling in the liver in both sexes compared to HFCN. Inflammatory activity showed predicted activation for females in the HFBN:HFCN comparison. In males, the inflammatory pathway molecular mechanisms of cancer was predicted as deactivated in HFBN:HFCN. (4) Dietary protein source impacts outcomes, and these outcomes improved with AHE. The HFBN diet improves signaling associated with lipid utilization for females and males, and improved inflammatory signaling for males compared with HFCN. Further exploration of AHE as a dietary intervention in high-fat diets is warranted. Full article

Background: Type 2 diabetes mellitus (T2DM) is a global epidemic in which gut microbiota dysbiosis contributes to impaired glucose homeostasis and chronic inflammation. Intermittent fasting (IF) and probiotic supplementation have independently demonstrated glycemic benefits in T2DM, largely through microbiota remodeling. This narrative review synthesizes evidence up to October 2025 to clarify the microbiota-dependent mechanisms of IF and probiotics, and to evaluate the biological plausibility and preliminary clinical data for their combined application in T2DM management. Methods: We conducted a comprehensive literature review of preclinical and clinical studies (PubMed, Embase, Web of Science, and Cochrane Library) examining IF regimens (primarily time-restricted feeding and 5:2 protocols) and multi-strain probiotics containing Lactobacillus and Bifidobacterium species in T2DM or relevant models. Mechanistic pathways, microbial compositional shifts, and metabolic outcomes were qualitatively synthesized, with emphasis on overlapping signaling (short-chain fatty acids, bile acids, GLP-1, and barrier function). Results: IF consistently increases Akkermansia muciniphila and, variably, Faecalibacterium prausnitzii abundance, restores microbial circadian rhythmicity, and enhances SCFA and secondary bile acid production. Multi-strain probiotics modestly reduce HbA1c (–0.3% to –0.6%) and fasting glucose, outperforming single-strain preparations. Both interventions converge on reduced endotoxaemia and improved intestinal integrity. Preclinical models indicate potential synergy, whereas the only direct human trial to date showed neutral results. Conclusions: IF and probiotics engage overlapping microbiota-mediated pathways, supporting their combined use as an adjunctive strategy in T2DM. Adequately powered randomized trials incorporating deep metagenomics, metabolomics, and hard clinical endpoints are now required to confirm additive or synergistic efficacy. Full article

Objectives: Erhuang Quzhi Formula (EQF) has been used for the treatment of non-alcoholic fatty liver disease (NAFLD). However, its active components and mechanistic basis remain unclear. This study aims to systematically identify the therapeutic material basis of EQF and to elucidate its potential mechanisms of action against NAFLD through an integrated multi-omics strategy. Methods: An integrated strategy combining UPLC-Q-TOF-MS and network pharmacology was applied to characterize serum components of EQF and construct a compound–target network. Core targets were screened and validated by molecular docking. A NAFLD model was established in C57BL/6 mice through high-fat diet feeding. To evaluate the therapeutic effects, mice were treated with EQF and assessed by measurements of serum biochemical parameters, liver histopathology, and glucose tolerance. UPLC-Q-TOF-based lipidomic and metabolomic analyses of liver tissue were conducted to clarify EQF’s regulatory effects on global lipid profiles and endogenous metabolites. Key genes and proteins involved in relevant signaling pathways were verified by RT-qPCR and Western blot. Results: A total of thirty-one prototype compounds were identified in the EQF-containing serum. Network pharmacology analysis predicted that EQF may alleviate NAFLD by acting on core targets such as TNF, JUN, and STAT3. In vivo experiments demonstrated that EQF administration significantly improved liver function, attenuated dyslipidemia, and reduced inflammation in model mice. Furthermore, metabolomic and lipidomic analyses indicated that EQF effectively reversed abnormal glycerophospholipid and sphingolipid levels and restored their metabolic homeostasis. Conclusions: EQF exerts therapeutic effects in a NAFLD mouse model through multi-component, multi-target, and multi-pathway mechanisms, primarily associated with the regulation of lipid metabolism, improvement of liver function, and suppression of inflammatory responses. This study provides mechanistic insights and a pharmacodynamic basis for the future clinical investigation of EQF. Full article

Background: The 2023 Delphi consensus defined metabolic and alcohol-associated liver disease (MetALD), distinguishing between alcohol abuse and moderate consumption. Although alcohol abuse is known to accelerate fatty liver disease progression, the health effects of chronic moderate alcohol intake under different dietary conditions remain unclear. This study aimed to evaluate the impact of moderate alcohol consumption on metabolic phenotypes and gut microbiota/metabolites in lean and obese mice and to propose a model approximating MetALD features. Methods: C57BL/6J mice were fed either a low-fat diet (LFD) or a high-fat diet (HFD) for 12 weeks, with access to 10% (v/v) alcohol in drinking water. Systemic metabolic parameters, liver histopathology, inflammatory and fibrotic markers, gut microbiota composition, and the fecal metabolome were assessed. Results: In LFD-fed mice, 10% alcohol intake induced multiple metabolic alterations, including elevated serum triglycerides, reduced fasting blood glucose, and changes in hepatic lipid metabolism along with steatosis and inflammation—though further studies are required to confirm causality. When combined with HFD, alcohol did not significantly exacerbate most glucose/lipid metabolic disorders but markedly increased hepatic inflammatory cell infiltration and fibrosis progression. Alcohol consistently increased gut microbial α-diversity in both dietary groups, while downregulating beneficial metabolites such as amino acids (e.g., glutamine, histidine), their derivatives, and short-chain fatty acids. Correlation analyses associated these microbial and metabolic changes with altered amino acid/cholesterol metabolism and inflammatory/fibrotic phenotypes, particularly under HFD conditions. Conclusions: These findings suggest that chronic moderate alcohol intake presents distinct risks in lean and obese individuals with different dietary structures. Full article

Background: Liver regeneration is essential for restoring hepatic mass after injury or resection, with metabolic reprogramming as a critical driver. Radix Rehmanniae Praeparata (RRP), a traditional Chinese medicine for chronic liver diseases, regulates glucose and lipid metabolism. This study evaluated the effects of RRP on liver regeneration and explored the underlying mechanisms. Methods: A 70% partial hepatectomy (PHx) mouse model was employed, and integrated transcriptomic and metabolomic analyses were conducted to characterize the global features of RRP-induced metabolic reprogramming and its association with hepatocyte proliferation. To further validate these findings, the AML12 hepatocyte cell line and primary mouse hepatocytes were used to identify key targets of RRP. Results: RRP significantly enhanced liver regeneration, as evidenced by the upregulation of hepatocyte proliferation markers. Transcriptomic, metabolomic, and biochemical analyses showed that RRP promoted lipid catabolism and H3K27ac remodeling-dependent hepatocyte proliferation by increasing acetyl-CoA flux. RRP also enhanced carbohydrate consumption and pentose phosphate pathway, as well as protecting mitochondrial integrity, which contribute to both energy production and nucleotide synthesis during cell cycle progression. Notably, RRP-induced AMPK activation was involved in these metabolic reprogramming events, since pharmacological inhibition of AMPK with Compound C attenuated the promotive effects of RRP on liver regeneration. Conclusions: RRP promotes liver regeneration by enhancing metabolic reprogramming mediated by AMPK activation, highlighting its therapeutic potential for metabolic adaptation and postoperative recovery in compromised liver. Full article

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease requiring multi-targeted therapeutic strategies. Gunnera perpensa and Erythrina zeyheri are traditionally used in diabetes management, but their mechanisms remain poorly understood. Methods: This study used in vitro, metabolomics, and network pharmacology approaches to elucidate their antidiabetic potential. Leaf extracts were screened for glucose utilization in C2C12 cells, and cytotoxicity in Vero cells. Metabolites profiled via GC×GC-TOF-MS and those retrieved from Phytochemical Interaction Database were evaluated for drug-likeness and target prediction using SwissADME and SwissTargetPrediction. Diabetes-related targets were obtained from databases, and overlapping targets were used to construct interaction networks using Cytoscape and STRING. Functional enrichment analyses were conducted via DAVID for GO and KEGG pathways. Results: G. perpensa acetone and methanol extracts enhanced superior glucose utilization (IC₅₀ = 78.5 and 94.8 µg/mL, respectively), with low cytotoxicity (LC₅₀ > 600 µg/mL). Key compounds including arabinose, identified from both plants, showed multi-target binding potential against STAT3, PIK3RI and JAK2. Enrichment analyses revealed pathways related to insulin signaling, inflammation, and glucose metabolism. Conclusions: This study supports the therapeutic relevance of phytochemical synergy in the traditional use of both plants and demonstrated systems-level approaches for elucidating complex drug–target interactions in T2DM. Full article

Cherry tomato is a notable dietary source of metabolites associated with antioxidant functions. However, how ripening reshapes primary, specialized, and volatile metabolites remains incompletely resolved. Green-ripe and red-ripe fruits were comparatively analyzed using targeted HPLC assays for quality indices and vitamins, UPLC–MS/MS for non-volatile metabolites, and HS-SPME–GC–MS for volatiles. Ripening was accompanied by a pronounced accumulation of lycopene and an increase in soluble solids, reflecting a shift of sugars toward glucose and fructose while sucrose remained low. Organic acids declined overall, with citric acid remaining predominant. The free-amino-acid pool expanded, with redistribution from GABA toward glutamate and aspartate. Vitamins exhibited stage-dependent patterns; antioxidant-related vitamins (A, E, and C) were higher at the red-ripe stage, indicating a compositional enhancement relevant to nutritional quality. Non-volatile metabolomics revealed 618 differentially accumulated metabolites, with phenolic acids, flavonoids, alkaloids, amino acids, and lipids as major classes. Phenolic acids and flavonols, dominated by hydroxycinnamoyl-quinic acids and quercetin/kaempferol glycosides, accumulated at the red-ripe stage, whereas steroidal glycoalkaloids decreased, suggesting conversion away from bitter or anti-nutritional constituents. GC–MS profiling identified 788 volatiles, with esters, terpenoids, and ketones contributing more than half of the volatilome. Ripening favored fruity–floral odorants such as β-ionone and (5Z)-octa-1,5-dien-3-one, while reducing green-leaf aldehydes. These stage-specific shifts in metabolite composition jointly define the sensory and nutritional maturation of cherry tomato. The identified metabolite markers provide a foundation for evaluating fruit maturity and guiding breeding toward improved quality attributes. Full article

Post-weaning diarrhea caused by Enterotoxigenic Escherichia coli (ETEC) is a major disease in piglets and leads to substantial economic losses in the swine industry. Compared to conventional lysozyme, yak stomach lysozyme (YSL) demonstrates distinctive resistance to pepsin, trypsin, high temperature, and acidic conditions. This study investigated the effects of dietary YSL supplementation on intestinal health in weaned piglets challenged with ETEC, utilizing metabolomics and proteomics. A total of 18 weaned piglets were randomly divided into three groups: control (C), diarrhea (D), and YSL treatment (YLT). Groups C and D were fed a basal diet, while the YLT group received the basal diet supplemented with YSL at a dosage of 100,000 U/kg following ETEC challenge. Following an acclimation period, piglets in groups D and YLT were orally challenged with ETEC, while group C received the same volume of sterile LB broth. The feeding trial lasted for 21 days before sample collection. The results demonstrated that dietary supplementation with YSL significantly reduced the diarrhea rate (p < 0.05). Compared with the D group, the YLT group exhibited significantly increased serum albumin levels (p < 0.05), along with a tendency toward greater villus height (p = 0.085) and higher serum glucose levels (p = 0.052), indicating an improvement in nutritional and metabolic status Metabolomic analysis identified 260 differentially abundant metabolites between the YLT and D groups (81 upregulated, 179 downregulated), which were predominantly enriched in pathways related to amino acid biosynthesis and metabolism, purine metabolism, and nucleic acid metabolism. Proteomic profiling revealed 571 differentially expressed proteins (237 upregulated, 334 downregulated). Upregulated proteins were mainly involved in arginine biosynthesis and base excision repair, while downregulated proteins were associated with the PPAR signaling pathway and Salmonella infection. In summary, dietary YSL supplementation alters the metabolic and proteomic profiles in the intestines of diarrheic piglets, potentially improving gut barrier function and nutrient utilization. This study offers novel insights into the potential of YSL as a promising feed additive for prevention of post-weaning diarrhea in pigs. Full article

Background/Objectives: To date, few studies have investigated the therapeutic effects of soy versus whey protein supplementation on obesity and insulin resistance (IR), yielding inconsistent findings. The aim of the present study was to compare the therapeutic efficacy of soy versus whey protein on obesity and IR and to elucidate their potential molecular mechanisms. Methods: Forty male C57BL/6J mice were randomly divided into two groups and fed either a normal diet (n = 8) or a high-fat diet (HFD, n = 32) for 16 weeks to induce obesity. After 16 weeks, HFD-induced obese mice were further randomized into three groups: HFD control, HFD + 20% whey protein isolate (WPI), and HFD + 20% soy protein isolate (SPI) for 6 weeks (n = 8). Results: Body weight, weight gain, body mass index, and Lee index showed no significant differences between the WPI and SPI groups. Compared with the WPI group, serum concentrations of insulin and leptin and the homeostasis model assessment of IR (HOMA-IR) were significantly lower, and thymus wet weight, fetal total cholesterol level, and serum glucose-dependent insulinotropic polypeptide concentration were significantly higher in the SPI group. Compared with the WPI group, the protein levels of GLUT4 and p-PI3K/PI3K were significantly higher in the SPI group. Metabolomics analysis showed that hepatic phosphocholine levels were significantly higher in the SPI group than in the WPI group. Moreover, hepatic differentially abundant metabolites of SPI- and WPI-fed mice were primarily enriched in the glycerophospholipid metabolism pathway. Conclusions: Soy protein was more effective than whey protein in ameliorating IR in HFD-induced obese mice, probably by modulating the PI3K-GLUT4 pathway and glycerophospholipid metabolism. Moreover, soy protein and whey protein showed comparable anti-obesity efficacy. Full article

Background/Objectives: The association between plasma metabolites derived from dietary substrates and inflammatory processes remains underexplored, despite its potential relevance in the prevention of non-communicable diseases. This systematic review aimed to examine the relationship between blood metabolites and the modulation of inflammatory biomarkers. Methods: A total of 25 randomized controlled trials, published between 2019 and 2024, were included from an initial pool of 111 records. These studies investigated the effects of dietary patterns, specific food groups, or nutritional supplements on the human metabolome and their potential links to inflammation. Results: Metabolomic analyses were predominantly performed using mass spectrometry (MS)-based platforms (17 out of 25), with liquid chromatography–mass spectrometry as the most frequently employed method. Both targeted (n = 14) and untargeted (n = 11) approaches were represented, and samples were drawn from plasma, urine, and feces. Across the interventions, 64 metabolites were modulated, including fatty acyls, glycerolipids, benzenoids, and organic acids, reflecting potential changes in pathways related to oxidative stress, lipid and carbohydrate metabolism, and inflammatory signaling. Several studies also assessed classical inflammatory biomarkers such as C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Interventions involving healthy traditional dietary patterns, improvements in dietary fat quality, or the use of specific probiotic strains were often associated with favorable immunometabolic outcomes. In contrast, some interventions, such as Mohana Choorna, elicited upregulation of immune-related gene expression in adipose tissue without improvements in glucose or lipid metabolism. Conclusions: While metabolomic responses varied across studies, the evidence highlights the value of dietary interventions in modulating systemic metabolism and inflammation. These findings support the integration of metabolomics into clinical nutrition to define more personalized and effective dietary strategies for inflammation-related chronic disease prevention. Full article

Influenced by various physical, chemical, and microbial factors, the aging process of Citri Reticulatae ‘Chachiensis’ Pericarpium (CRCP) poses a complex scientific challenge. Drawing inspiration from the perspective of traditional Chinese medicine, volatile oils were extracted from CRCP aged 1, 3, 5, and 7 years by steam distillation and subsequently analyzed by GC-MS. The results revealed that the relative percentage of 4-vinylguaiacol (4-VG) increased progressively with aging. Nineteen volatile oil components were further assessed for their glucose metabolism-enhancing activities, with 4-VG emerging as a key active compound. Notably, 4-VG remarkably enhanced insulin-stimulated glucose uptake in C2C12 myotubes. Moreover, 4-VG demonstrated potent antihyperglycemic effects by upregulating IRS-1/Akt/GSK-3β phosphorylation in the insulin signaling pathway on a high-fat diet and STZ-induced diabetic mouse model. In addition, the metabolic pathway of 4-VG, from ferulic acid and then to vanillin and guaiacol, was verified via HPLC-UV, metabolomics, and microbiome analyses, which confirmed the microbial conversion of 4-VG within CRCP. The metabolic pathway was ultimately validated by isolating and identifying Priestia aryabhattai, Bacillus velezensis, and Aspergillus fumigatus from CRCP, with further in vitro culture and biotransformation experiments confirming its functionality and efficiency. These findings provide new insights and experimental evidence that deepen our understanding of the aging process of CRCP. Full article

The aim of the present study is to evaluate the impact of chromium (Cr) supplementation on glucose and lipid metabolism in breast muscle in broilers under heat stress. A total of 220 day-old broiler chicks were reared in cages. At 29 days old, 180 birds were randomly assigned to three treatments (0, 400, and 800 µg Cr/kg, as chromium picolinate) and transferred to climate chambers (31 ± 1 °C, 60 ± 7% humidity) for 14 days. Growth performance, carcass traits, serum biochemical indices, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), as well as muscle metabolomic profiles and gene expression related to energy and lipid metabolism were analyzed. The results showed that, compared with the heat stress group, the groups supplemented with 400 and 800 µg Cr/kg showed higher dry matter intake and average daily gain, breast muscle ratio, and lower feed conversion ratio and abdominal fat ratio; chickens supplemented with 400 and 800 µg Cr/kg showed significantly lower serum corticosterone (CORT), free fatty acids, and cholesterol levels compared with the heat stress (HS) group (p < 0.05). Fasting blood glucose and HOMA-IR were also significantly reduced, while fasting insulin was significantly increased in the Cr-supplemented groups (p < 0.05). Metabolomic analysis revealed that Cr supplementation regulated lipid and amino acid metabolism by altering key metabolites such as citric acid, L-glutamine, and L-proline, and modulating pathways including alanine, aspartate, and glutamate metabolism, and glycerophospholipid metabolism. Furthermore, Cr supplementation significantly upregulated the expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 α (PGC-1α), ATP Binding Cassette Subfamily A Member 1 (ABCA1), Peroxisome Proliferator-Activated Receptor α (PPARα), and ATP Binding Cassette Subfamily G Member 1 (ABCG1) in both the hepatic and muscle tissue. This paper suggested that chromium supplementation may enhance energy metabolism and lipid transport like the findings of our study suggested. Full article