Functional effects of virgin flaxseed oil on nutrigenomics regulation in a rat model of obesity

Abstract

Background

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with altered lipid metabolism, inflammation, and increased cardiovascular risk.

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with altered lipid metabolism, inflammation, and increased cardiovascular risk.

Objective

This study evaluated the nutrigenomic effects of diets containing virgin flaxseed oil (VFO), compared with animal fat and soybean oil, on metabolic parameters, hepatic fatty acid (FA) profile, and expression of genes involved in lipid metabolism in diet-induced obese rats.

This study evaluated the nutrigenomic effects of diets containing virgin flaxseed oil (VFO), compared with animal fat and soybean oil, on metabolic parameters, hepatic fatty acid (FA) profile, and expression of genes involved in lipid metabolism in diet-induced obese rats.

Methods

Male Wistar rats received for 90 days either a control diet containing 4% soybean oil (S4, n = 6) or an obesogenic diet containing 20% fructose and 20% animal fat (OB, n = 24). Ethics Committees: # CE2020-64. At the end of this period, six animals from S4 and six from OB were euthanized. Remaining OB animals continued for 60 additional days with diets containing 4% soybean oil, animal fat, or VFO, forming OBS4 (n = 6), OBGA4 (n = 6), and OBVFO4 (n = 6). Anthropometric parameters, serum and hepatic triglycerides (TG), hepatic FA profile, and gene expression of enzymes and transcription factors were assessed by RT-qPCR.

Male Wistar rats received for 90 days either a control diet containing 4% soybean oil (S4, n = 6) or an obesogenic diet containing 20% fructose and 20% animal fat (OB, n = 24). Ethics Committees: # CE2020-64. At the end of this period, six animals from S4 and six from OB were euthanized. Remaining OB animals continued for 60 additional days with diets containing 4% soybean oil, animal fat, or VFO, forming OBS4 (n = 6), OBGA4 (n = 6), and OBVFO4 (n = 6). Anthropometric parameters, serum and hepatic triglycerides (TG), hepatic FA profile, and gene expression of enzymes and transcription factors were assessed by RT-qPCR.

Results

After 90 days, the OB diet increased energy intake, body weight, adipose tissue mass, and serum and hepatic TG levels (P < 0.05 vs. S4). At the hepatic level, reduced flux through stearoyl-CoA desaturase-1 (SCD1) was evidenced by decreased palmitoleic/palmitic and oleic/stearic acid ratios, along with an increased arachidonic acid/eicosapentaenoic acid ratio. In addition, decreased expression of genes involved in lipogenesis (FAS, ACC, and SCD1) and FA oxidation (ACOX1 and CPT1a) were observed, together with increased expression of the FA transporter FATP2. Following the intervention, VFO significantly reduced serum and hepatic TG, improved the hepatic FA profile (higher α-linolenic acid/linoleic acid ratio and lower arachidonic acid/eicosapentaenoic acid ratio), and modulated hepatic gene expression by decreasing SREBP1c, FAS, SCD1, and SREBP1a, while increasing PPARα expression.

After 90 days, the OB diet increased energy intake, body weight, adipose tissue mass, and serum and hepatic TG levels (P < 0.05 vs. S4). At the hepatic level, reduced flux through stearoyl-CoA desaturase-1 (SCD1) was evidenced by decreased palmitoleic/palmitic and oleic/stearic acid ratios, along with an increased arachidonic acid/eicosapentaenoic acid ratio. In addition, decreased expression of genes involved in lipogenesis (FAS, ACC, and SCD1) and FA oxidation (ACOX1 and CPT1a) were observed, together with increased expression of the FA transporter FATP2. Following the intervention, VFO significantly reduced serum and hepatic TG, improved the hepatic FA profile (higher α-linolenic acid/linoleic acid ratio and lower arachidonic acid/eicosapentaenoic acid ratio), and modulated hepatic gene expression by decreasing SREBP1c, FAS, SCD1, and SREBP1a, while increasing PPARα expression.

Conclusion

Overall, these findings suggest a hepatoprotective and anti-inflammatory effect of VFO, possibly mediated by n-3 FA and their derivatives, whichpleiotropically regulate genes involved in lipid synthesis and oxidation pathways.

Overall, these findings suggest a hepatoprotective and anti-inflammatory effect of VFO, possibly mediated by n-3 FA and their derivatives, whichpleiotropically regulate genes involved in lipid synthesis and oxidation pathways.