Obesity and its associated metabolic disorders are closely linked to chronic inflammation, oxidative stress, and intestinal dysfunction induced by high-fat diet (HFD).Systematically evaluated the intervention effects of α-linolenic acid (ALA), conjugated linoleic acid (CLA), and oleic acid (OA) on HFD-induced metabolic disorders in obese mice.C57BL/6 J mouse model was established with a high-fat diet and divided into the following groups, including control group (Con), HFD group, eicosapentaenoic acid (EPA) positive control group, and ALA, CLA, or OA intervention groups (n=8 per group).After 4 weeks of intervention, the weight, lipid levels, intestinal tissue morphology, and levels of inflammation and oxidative stress in mice were analyzed.The results indicated that both ALA and EPA significantly inhibited weight gain, reduced the serum and liver TC, TG, and LDL-C levels and increased the HDL-C levels.Furthermore, these fatty acids reversed the shortening of intestinal villi caused by HFD, increased the villus-crypt ratio, inhibited the expression of small intestinal inflammatory factors TNF-α and IL-1β, and improved the oxidative stress by increasing superoxide dismutase, glutathione, and catalase activities while decreasing malondialdehyde content.In contrast, interventions with CLA or OA had no significant regulatory effect.The study demonstrated that ALA had anti-obesity properties along with protective effects on the small intestine.These findings provide a foundation for precise dietary lipid regulation in addressing metabolic syndrome.
[1] HOTAMISLIGIL G S.Inflammation, metaflammation and immunometabolic disorders[J].Nature, 2017, 542(7640):177-185.
[2] HOTAMISLIGIL G S.Inflammation and metabolic disorders[J].Nature, 2006, 444(7121):860-867.
[3] CALDER P C.Marine omega-3 fatty acids and inflammatory processes:Effects, mechanisms and clinical relevance[J].Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 2015, 1851(4):469-484.
[4] BORK C S, LARSEN J M, LUNDBYE-CHRISTENSEN S, et al.Plant omega-3 fatty acids may lower risk of atrial fibrillation in individuals with a low intake of marine omega-3 fatty acids[J].The Journal of Nutrition, 2024, 154(9):2827-2833.
[5] OUYANG J, LI X P, LIU C W, et al.Junshanyinzhen tea extract prevents obesity by regulating gut microbiota and metabolic endotoxemia in high-fat diet fed rats[J].Food Science and Human Wellness, 2024, 13(4):2036-2047.
[6] PRASHANTH V, DEVARAJAN A K, PERUMAL M K.Morin attenuates high-fat diet induced inflammation and enhances the Akkermansiaceae richness in the gut of C57BL/6 J mice[J].Food Bioscience, 2025, 66:106153.
[7] CANI P D, BIBILONI R, KNAUF C, et al.Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J].Diabetes, 2008, 57(6):1470-1481.
[8] CAI Y, DENG W L, YANG Q P, et al.High-fat diet-induced obesity causes intestinal Th17/Treg imbalance that impairs the intestinal barrier and aggravates anxiety-like behavior in mice[J].International Immunopharmacology, 2024, 130:111783.
[9] LI X, HUANG G W, ZHANG Y N, et al.Succinate signaling attenuates high-fat diet-induced metabolic disturbance and intestinal barrier dysfunction[J].Pharmacological Research, 2023, 194:106865.
[10] BISCHOFF S C, BARBARA G, BUURMAN W, et al.Intestinal permeability:A new target for disease prevention and therapy[J].BMC Gastroenterology, 2014, 14:189.
[11] FUKUI H.Increased intestinal permeability and decreased barrier function:Does it really influence the risk of inflammation?[J].Inflammatory Intestinal Diseases, 2016, 1(3):135-145.
[12] KIM K A, GU W, LEE I A, et al.High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway[J].PLoS One, 2012, 7(10):e47713.
[13] AKOUMIANAKIS I, ANTONIADES C.Impaired vascular redox signaling in the vascular complications of obesity and diabetes mellitus[J].Antioxidants & Redox Signaling, 2019, 30(3):333-353.
[14] LI S R, EGUCHI N, LAU H, et al.The role of the Nrf2 signaling in obesity and insulin resistance[J].International Journal of Molecular Sciences, 2020, 21(18):6973.
[15] MARSEGLIA L, MANTI S, D'ANGELO G, et al.Oxidative stress in obesity:A critical component in human diseases[J].International Journal of Molecular Sciences, 2014, 16(1):378-400.
[16] HAGHIGHATDOOST F, NOBAKHT M GH B F.Effect of conjugated linoleic acid on blood inflammatory markers:A systematic review and meta-analysis on randomized controlled trials[J].European Journal of Clinical Nutrition, 2018, 72(8):1071-1082.
[17] LIANG C W, CHENG H Y, LEE Y H, et al.Effects of conjugated linoleic acid and exercise on body composition and obesity:A systematic review and meta-analysis[J].Nutrition Reviews, 2023, 81(4):397-415.
[18] FUSSBROICH D, COLAS R A, EICKMEIER O, et al.A combination of LCPUFA ameliorates airway inflammation in asthmatic mice by promoting pro-resolving effects and reducing adverse effects of EPA[J].Mucosal Immunology, 2020, 13(3):481-492.
[19] FUJITA Y, KANO K, KISHINO S, et al.Dietary Cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer's disease mouse model[J].Scientific Reports, 2021, 11(1):9749.
[20] ZHENG J N, CHEN S M, LIU L, et al.In vitro gastrointestinal digestibility and lipid oxidation of fish oil-in-water emulsions:Influence of different EPA/DHA ratios[J].LWT, 2024, 210:116855.
[21] DASILVA G, BOLLER M, MEDINA I, et al.Relative levels of dietary EPA and DHA impact gastric oxidation and essential fatty acid uptake[J].The Journal of Nutritional Biochemistry, 2018, 55:68-75.
[22] EL-MOWAFY A M, ABDEL-AZIZ A A, ABDEL-DAYEM M A.Novel protection by omega-3-FAs (DHA or EPA) against carbamazepine's liver-injury:Differential suppression of oxidative-stress and inflammatory markers, and the influence on carbamazepine-clearance[J].Clinical Nutrition Open Science, 2022, 42:14-26.
[23] SHERRATT S, LIBBY P, BHATT D, et al.Eicosapentaenoic acid (EPA) modulated expression of endothelial proteins linked to detoxification and inhibition of oxidative stress during inflammation[J].Atherosclerosis, 2023, 379:S2-S3.
[24] SHERRATT S C R, LIBBY P, BHATT D L, et al.Eicosapentaenoic acid (EPA) combined with high-intensity statins reduce lipid oxidation in model membranes compared to docosahexaenoic acid (DHA)[J].Atherosclerosis, 2022, 355:93.
[25] YANG X, LI X D, HU M J, et al.EPA and DHA differentially improve insulin resistance by reducing adipose tissue inflammation:Targeting GPR120/PPARγ pathway[J].The Journal of Nutritional Biochemistry, 2024, 130:109648.
[26] ZHANG X W, LI C, REN W Z, et al.Omega-3 polyunsaturated fatty acids, especially DHA and EPA, remold gut microbiota to suppress inflammation in rabbits with atherosclerosis[J].Animals and Zoonoses, 2025,1(2): 122-130.
[27] JUMP D B.The biochemistry of n-3 polyunsaturated fatty acids[J].Journal of Biological Chemistry, 2002, 277(11):8755-8758.
[28] COSTANTINI L, MOLINARI R, FARINON B, et al.Impact of omega-3 fatty acids on the gut microbiota[J].International Journal of Molecular Sciences, 2017, 18(12):2645.
[29] HUANG J W, WANG X Y, XIE L Y, et al.Extract of Danggui-Shaoyao-San ameliorates cognition deficits by regulating DHA metabolism in APP/PS1 mice[J].Journal of Ethnopharmacology, 2020, 253:112673.
[30] ZENG Y Y, JIANG W D, LIU Y, et al.Dietary alpha-linolenic acid/linoleic acid ratios modulate intestinal immunity, tight junctions, anti-oxidant status and mRNA levels of NF-κB p65, MLCK and Nrf2 in juvenile grass carp (Ctenopharyngodon idella)[J].Fish & Shellfish Immunology, 2016, 51:351-364.
[31] KALIANNAN K, WANG B, LI X Y, et al.Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity[J].International Journal of Obesity, 2016, 40(6):1039-1042.
[32] TERÉS S, BARCELÓ-COBLIJN G, BENET M, et al.Oleic acid content is responsible for the reduction in blood pressure induced by olive oil[J].PNAS, 2008, 105(37):13811-13816.