Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice

January 1, 2009 Human Health and Nutrition Data 0 Comments

Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice

Year: 2009
Authors: Kelley, D.S. Vemuri, M. Adkins, Y. Gill, S.H.S. Fedor, D. Mackey, B.E.
Publication Name: British Journal of Nutrition
Publication Details: Volume 101, Pages 701-708.


Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30% of US adults, respectively. Trans-10, cis12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5%) or CLA and flaxseed oil (FSO) (0.5%) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 forb cell function were higher by 160, 636, 985 and 968% in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20% and liver weights by 37% compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 forb cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73% and increased the n-6:n-3 ratio by 58% compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342% and decreased the n-6:n-3 ratio by 70% compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid (ALA), 18:3n-3. (Authors abstract)

Insulin resistance (IR) is a condition in which normal amounts of insulin are inadequate to produce normal responses from fat, muscle (promote glucose uptake) and liver (inhibit glucose output) cells. IR is critical in in the development of type 2 diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) and CVD. NAFLD encompasses includes simple TAG accumulation in hepatocytes (hepatic steatosis) and inflammation (steatohepatitis), fibrosis and cirrhosis. Frequently NAFLD and IR are associated with obesity, type 2 diabetes mellitus and dyslipidaemia.  Dietary factors that contribute to the development of IR and NAFLD include high-fat (saturated and trans-fatty acids). One of the trans-fatty acids isconjugated linoleic acid (CLA) which is linoleic acid isomers having conjugated double bonds. The investigators indicate that  amounts of trans-10, cis-12-CLA consumed alone or along with other trans fatty acids from partially hydrogenated or processed foods can reach levels beyond what is needed to induce IR and NAFLD.  Trans-10, cis-12-CLA has been shown in animal work to reduce depot fats while causing fatty liver and IR. It also increased the liver concentrations of oleic acid (18:1n-9) and decreased those of n-6 and n-3 PUFA. NAFLD is associated with an increase in the hepatic n-6:n-3 ratio (31). The investigators propose that the aggravation of n-3 PUFA inadequacy (increased ratio between n-6 and n-3 PUFA) by CLA exacerbates the development of fatty liver and IR; these CLA-induced pathologies could be prevented by the concomitant increase in the intake of n-3 PUFA. Supplementing diets of obese rats and mice with alpha-linolenic acid (ALA; 18:3n-3) prevented the development of NAFLD and IR. It also prevented a sucrose-induced IR in non-obese rats. Thus the objective of the present study was to determine if ALA will prevent the development of fatty liver and IR induced by CLA. The present results demonstrate that the small amount of ALA (0.3g/100g diet) from FSO completely prevented the CLA induced IR and significantly decreased the fasting plasma glucose concentration. It also significantly reduced the development of fatty liver; however, it was not a complete prevention. The disparity of the effects of ALA on fatty liver and IR may suggest the involvement of different mechanism(s) or that a higher concentration of ALA may be needed to completely prevent the CLA-induced fatty liver than that required to prevent IR. Prevention of CLA-induced IR by ALA was associated with reversal of the changes in liver fatty acid composition induced by CLA. Dietary FSO increased the hepatic concentration of n-6 PUFA (linoleic acid, arachidonic acid and docosapentaenoic acid) and n-3 PUFA (ALA, EPA and DHA) and it decreased the n-6:n-3 PUFA ratio by 71%. The most dramatic increases were in the concentrations of ALA and DHA, which most probably was the basis for improved insulin sensitivity. The investigators postulate that the prevention of IR and NAFLD in the present study resulted from the increase in liver concentration of n-3 and not n-6 PUFA. Further studies with increasing concentrations of DHA and ALA are needed to determine the minimum dose of the n-3 PUFA needed to prevent the NAFLD and IR induced by a known concentration of trans-10,cis-12-CLA. In addition, the underlying mechanism(s) by which CLA increased and ALA reduced the plasma insulin concentrations are not known. (Editors comments)

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