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A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats.

Abstract

Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA¹:¹), or low n-3/n-6 PUFA ratio (1∶4, PUFA¹:⁴). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA¹:¹ diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA¹:¹ compared with SFA; however, PUFA¹:⁴ diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA¹:¹ diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines.

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  • Authors+Show Affiliations

    ,

    Department of Nutrition and Food Hygiene and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.

    , , , , , , , , , ,

    Source

    Nutrition research (New York, N.Y.) 33:10 2013 Oct pg 849-58

    MeSH

    Animals
    C-Reactive Protein
    Dietary Fats
    Down-Regulation
    Fatty Acids
    Fatty Acids, Omega-3
    Fatty Acids, Omega-6
    Glucose Intolerance
    Inflammation
    Insulin Resistance
    Interleukin-6
    Intra-Abdominal Fat
    Lipids
    Male
    Obesity
    RNA, Messenger
    Rats
    Rats, Sprague-Dawley
    Toll-Like Receptor 4
    Tumor Necrosis Factor-alpha
    Weight Loss

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24074743

    Citation

    Liu, Han-Qiang, et al. "A High Ratio of Dietary N-3/n-6 Polyunsaturated Fatty Acids Improves Obesity-linked Inflammation and Insulin Resistance Through Suppressing Activation of TLR4 in SD Rats." Nutrition Research (New York, N.Y.), vol. 33, no. 10, 2013, pp. 849-58.
    Liu HQ, Qiu Y, Mu Y, et al. A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats. Nutr Res. 2013;33(10):849-58.
    Liu, H. Q., Qiu, Y., Mu, Y., Zhang, X. J., Liu, L., Hou, X. H., ... Wang, F. (2013). A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats. Nutrition Research (New York, N.Y.), 33(10), pp. 849-58. doi:10.1016/j.nutres.2013.07.004.
    Liu HQ, et al. A High Ratio of Dietary N-3/n-6 Polyunsaturated Fatty Acids Improves Obesity-linked Inflammation and Insulin Resistance Through Suppressing Activation of TLR4 in SD Rats. Nutr Res. 2013;33(10):849-58. PubMed PMID: 24074743.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats. AU - Liu,Han-Qiang, AU - Qiu,Ya, AU - Mu,Ying, AU - Zhang,Xian-Jiao, AU - Liu,Lu, AU - Hou,Xiang-Hong, AU - Zhang,Lei, AU - Xu,Xiao-Na, AU - Ji,Ai-Ling, AU - Cao,Rui, AU - Yang,Rui-Hua, AU - Wang,Feng, Y1 - 2013/08/09/ PY - 2012/12/13/received PY - 2013/06/27/revised PY - 2013/07/04/accepted PY - 2013/10/1/entrez PY - 2013/10/1/pubmed PY - 2014/4/5/medline KW - C-reactive protein KW - CRP KW - DHA KW - EPA KW - H&E KW - HOMA-IR KW - IKK-β KW - IL-6 KW - IR KW - IRS KW - ITT KW - Insulin resistance KW - IκB kinase β KW - LPS KW - MyD88 KW - NF-κB KW - PCR KW - PUFAs KW - Polyunsaturated fatty acids KW - Pro-inflammatory cytokines KW - Rat KW - SFA KW - T2DM KW - TC KW - TG KW - TIR domain-containing adaptor inducing interferon β KW - TLR KW - TNF-α KW - TRAM KW - TRIF KW - TRIF-related adaptor molecule KW - Toll-like receptor-4 KW - docosahexanoic acid KW - eicosapentaenoic acid KW - hematoxylin and eosin KW - homeostasis model assessment of insulin resistance KW - insulin receptor substrate KW - insulin resistance KW - insulin tolerance test KW - interleukin-6 KW - lipopolysaccharide KW - myeloid differentiation factor-88 KW - nuclear factor κB KW - polymerase chain reaction KW - polyunsaturated fatty acids KW - saturated fatty acid KW - toll-like receptor KW - total cholesterol KW - triglycerides KW - tumor necrosis factor α KW - type 2 diabetes mellitus SP - 849 EP - 58 JF - Nutrition research (New York, N.Y.) JO - Nutr Res VL - 33 IS - 10 N2 - Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA¹:¹), or low n-3/n-6 PUFA ratio (1∶4, PUFA¹:⁴). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA¹:¹ diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA¹:¹ compared with SFA; however, PUFA¹:⁴ diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA¹:¹ diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines. SN - 1879-0739 UR - https://www.unboundmedicine.com/medline/citation/24074743/A_high_ratio_of_dietary_n_3/n_6_polyunsaturated_fatty_acids_improves_obesity_linked_inflammation_and_insulin_resistance_through_suppressing_activation_of_TLR4_in_SD_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0271-5317(13)00167-X DB - PRIME DP - Unbound Medicine ER -