The Alpha Linolenic Acid Content of Flaxseed is Associated with an Induction of Adipose Leptin Expression

Dietary flaxseed has cardioprotective effects that may be achieved through its rich content of the omega 3 fatty acid, alpha linolenic acid (ALA). Because ALA can be stored in adipose tissue, it is possible that some of its beneficial actions may be due to effects it has on the adipose tissue. We investigated the effects of dietary flaxseed both with and without an atherogenic cholesterol enriched diet to determine the effects of dietary flaxseed on the expression of the adipose cytokines leptin and adiponectin. Rabbits were fed one of four diets: a regular (RG) diet, or a regular diet with added 0.5% cholesterol (CH), or 10% ground flaxseed (FX), or both (CF) for 8 weeks. Levels of leptin and adiponectin expression were assessed by RTPCR in visceral adipose tissue. Consumption of flaxseed significantly increased plasma and adipose levels of ALA. Leptin protein and mRNA expression were lower in CH animals and were elevated in CF animals. Changes in leptin expression were strongly and positively correlated with adipose ALA levels and inversely correlated with levels of atherosclerosis. Adiponectin expression was not significantly affected by any of the dietary interventions. Our data demonstrate that the type of fat in the diet as well as its caloric content can specifically influence leptin expression. The findings support the hypothesis that the beneficial cardiovascular effects associated with flaxseed consumption may be related to a change in leptin expression. (Authors abstract)
Adipocytes secrete a number of important cellular signaling molecules, termed adipokines. These adipokines have consequences ranging from local autocrine and paracrine effects to systemic endocrine actions. Adipokines modulate the fatty acid composition of adipose tissue which can affect cellular signaling, fatty acid trafficking, gene expression and, consequently, metabolism. Adiponectin is the most highly expressed and secreted adipokine, with beneficial effects on metabolism, inflammation, and vascular function. Adiponectin plays a role in insulin sensitivity, LDL oxidation, eNOS activation, inflammation suppression and fatty acid catabolism.  Another important adipokine that could be stimulated by changes in fatty acid profile is leptin. Leptin plays a role in hypothalamic-mediated appetite suppression in response to caloric intake.  In obesity, leptin may be under-expressed by the adipose tissue in response to a consistently high caloric diet, or, leptin receptors may be down-regulated, thus leading to high plasma leptin levels and leptin resistance. Previous data have indicated that ALA from a flaxseed enriched diet is deposited in adipose tissue. In this study, the authors hypothesize that the change in lipid composition in adipose tissue in response to a flaxseed supplemented diet may affect the adipokine signaling from the adipocytes. It is possible, therefore, that the beneficial cardiovascular actions of flaxseed previously observed may be associated with changes in adipokine expression. One of the primary purposes of this study was to determine if diets of very different lipid composition could influence the expression of leptin or adiponectin in adipose tissue when caloric balance was maintained. The data obtained in the present study demonstrates that the lipid composition of the diet can have an important role to play in adipokine expression. A high cholesterol diet suppressed leptin expression whereas a diet rich in ALA increased leptin expression. Leptin expression was influenced by the diets whereas adiponectin was not. This data indicates that in a non-obese population, leptin may have a previously unidentified role in cardioprotection. In support of this hypothesis, leptin expression was significantly correlated in a negative fashion with atherosclerosis. When leptin levels were high, atherosclerosis was low and when leptin expression was depressed by circulating cholesterol, atherogenesis was stimulated. Dietary flaxseed provided a source of ALA in the present study which subsequently increased ALA both in the circulation and in the adipose tissue. Further study is required to understand the relative lack of storage of ALA in the adipose tissue when it is presented with such high levels of circulating ALA. The present data demonstrate that dietary cholesterol and flaxseed have the capacity to alter leptin expression.
In the present study, ALA in the adipose tissue was strongly associated with increased leptin expression and the subsequent reduction of atherosclerosis. This data suggests that flaxseed may induce its anti-atherogenic effects in part via an ALA-mediated modulation of the expression of leptin. (Editors comments)