Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes

Haiwen Li; Ahmed Reza Rafie; Anwar Hamama; Rafat A Siddiqui

doi:10.29219/fnr.v67.9126

Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes

Food Nutr Res. 2023 Mar 2:67. doi: 10.29219/fnr.v67.9126. eCollection 2023.

Authors

Haiwen Li¹, Ahmed Reza Rafie², Anwar Hamama³, Rafat A Siddiqui¹

Affiliations

¹ Food Chemistry and Nutrition Science Laboratory, Agricultural Research Station, College of Agriculture, Virginia State University, Petersburg, VA, USA.
² Cooperate Extension, College of Agriculture, Virginia State University, Petersburg, VA, USA.
³ Common Research Laboratory, Agricultural Research Station, College of Agriculture, Virginia State University, Petersburg, VA, USA.

Abstract

Background: Obesity is the underlying risk factor for major metabolism complications, including non-alcoholic-fatty liver disease, atherosclerosis, and cardiovascular disease. The adipose tissue is a vital endocrine organ that plays a role in the synthesis and storage of lipid and, therefore, is a contributory factor to the development and progression of obesity. A growing interest in nutraceuticals suggests that natural products can alleviate the risk factors and may be effective in mitigating obesity.

Aim: The objective of this study was to examine the underlying mechanisms of immature ginger on adipocyte differentiation and lipogenesis in a 3T3-L1 cellular model.

Methods: Ginger samples, extracted in 80% methanol, were dried and resuspended in DMSO at 50 μg/mL as stock solution. For analysis, the extracted samples were further diluted in media. Effects on adipogenesis were evaluated by determining lipid droplet and triglyceride accumulation, whereas effects on lipogenesis were determined by measuring triglyceride contents and fatty acid profile. The expression of key regulatory genes involved in adipogenesis and lipogenesis was also determined.

Results: Our data indicate that the intracellular lipid accumulation decreased significantly by 15 or 25% on treatment with 25 or 50 μg/mL of ginger extract. Consistent with these data, significantly reduced triglyceride levels by 30 or 50% were observed on 25 or 50 μg/mL treatment with ginger extracts, respectively. In addition, ginger treatment significantly inhibited the differentiation-induced de novo lipogenesis and Δ9 desaturase activity. Furthermore, ginger treatment reduced adipogenesis genes, C/ebpβ and C/ebpδ, expression by 47 or 64%, respectively, but significantly increased Pparγ expression by 60% and adiponectin by 75%. Ginger extracts had no effect on Fas genes but reduced lipogenesis genes, acyl CoA carboxylase (Acc) expression by two-fold, and phosphoenolpyruvate carboxy kinase 1 (Pepck1) expression by 50%.

Conclusion: Our findings suggest immature ginger can potentially inhibit lipogenesis pathways by limiting the channeling of glucose carbon in fatty acid synthesis by inhibiting the expression of ACC and glycerol production via inhibiting the expression of PEPCK, which consequently inhibits triglyceride formation.

Keywords: adipogenesis; fatty acids; glucose uptake; lipid droplets; lipogenesis; obesity.