Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

Abstract

Purpose and background The focus was directed to the study of two of the most lignan-rich food sources: sesame and flaxseeds. Recent epidemiological and experimental evidences suggesting that these foods may improve metabolic functions underlying metabolic syndrome (MetS). Methods To characterize the effect of these oilseeds on metabolic functions, we conducted an experimental study aimed at preventing adiposity and metabolic imbalance in a mouse model of high-fat diet (HFD)-induced MetS. Statistical analysis was performed by two-way analysis of variance test followed by post hoc Bonferroni analysis. Results We studied the effect of the oilseeds sesame and flaxseed on metabolic parameters in mice on a HFD. When the HFD was integrated with 20 % of sesame or flaxseed flours, the mice showed a decrease in body fat, already at day 15, from time 0. The size of the adipocytes was smaller in epididymal fat, liver steatosis was inhibited, and insulin sensitivity was higher in mice on the supplemented diets. The supplemented diets also resulted in a significant increase in the serum levels of the lignan metabolites enterodiol and enterolactone compared with the controls. The expression of genes associated with the inflammatory response, glucose metabolism, adipose metabolism and nuclear receptor were altered by the oilseed-supplemented diets. Some of the most abundant lignans in these oilseeds were studied in 3T3-L1 preadipocyte cells and were effective in inhibiting adipocyte differentiation at the minimal dose of 1 nM. Conclusions The consumption of sesame and flaxseed may be beneficial to decrease metabolic parameters that are generally altered in MetS.

7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6 mice on a high-fat diet

“…In conclusion, this work adds novel information to what has been found for other lignans in similar models ( 4 , 13 , 49 , 50 ) and highlights the physiological relevance of 7-HMR from nutraceutical and nutritional sources.…”

“…7-Hydroxymatairesinol (7-HMR) is a dibenzylbutyrolactone plant lignan closely related to matairesinol. It is found at relatively high concentrations in the heartwood of branches and knots of Norway spruce trees (Picea abies) (12) and in various concentrations in plant foods (10)(11)(12)(13)(14) . The activity and metabolism of 7-HMR has been recently evaluated in rats and in humans, with enterolactone (ENL) being the major metabolite identified (15,16) .…”

Cereal Lignans, Natural Compounds of Interest for Human Health?

“…A few cereal lignans have also been tested in vitro and found to be effective inhibitors of adipocyte differentiation. Pinoresinol, cycloisolariciresinol, lariciresinol, seicoisolariciresinol in the concentration range of 1-1000 nM, are effective in inhibiting 3T3-L1 cell differentiation [77] and although their fine mechanism of action has still to be clarified, it is likely that it involves the ability to regulate nuclear receptors such as PPARs, ERs and LXRs [65,78,79].…”

The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites

“…While lariciresinol ( 8g ) was found somewhat more active than secoisolariciresinol ( 8 ), with IC 50 values of 51.8 and 87.6 µM, respectively, this is a minor difference with little if any relevance in terms of a RONS‐scavenging related bioactivity change . However, much larger differences in the inhibitory activities of 8g and 8 can be observed on differentiation and fat accumulation of adipocytes (IC 50 < 10 nM for 8g vs. IC 50 > 100 nM for 8 ) . These 1 to 2 orders of magnitude difference in potency means that even small amounts of 8g formed from 8 may significantly modulate the overall bioactivity, perhaps in an oxidative stress‐related manner.…”

“…196 However, much larger differences in the inhibitory activities of 8g and 8 can be observed on differentiation and fat accumulation of adipocytes (IC 50 < 10 nM for 8g vs. IC 50 > 100 nM for 8). 197 These 1 to 2 orders of magnitude difference in potency means that even small amounts of 8g formed from 8 may significantly modulate the overall bioactivity, perhaps in an oxidative stress-related manner. Nevertheless, 8g formed through the oxidation of 8, can still be metabolized to the same end-products as its parent compound.…”