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

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 c...

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Main Authors: Haiwen Li, Ahmed Reza Rafie, Anwar Hamama, Rafat A. Siddiqui
Format: Article
Language:English
Published: Swedish Nutrition Foundation 2023-03-01
Series:Food & Nutrition Research
Subjects:
Online Access:https://foodandnutritionresearch.net/index.php/fnr/article/view/9126/15367
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author Haiwen Li
Ahmed Reza Rafie
Anwar Hamama
Rafat A. Siddiqui
author_facet Haiwen Li
Ahmed Reza Rafie
Anwar Hamama
Rafat A. Siddiqui
author_sort Haiwen Li
collection DOAJ
description 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.
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spelling doaj.art-a55af0fdb6f4414181ca0d902ecfee302023-04-08T15:53:09ZengSwedish Nutrition FoundationFood & Nutrition Research1654-661X2023-03-016711810.29219/fnr.v67.91269126Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytesHaiwen Li0Ahmed Reza Rafie1Anwar Hamama2Rafat A. Siddiqui3Food Chemistry and Nutrition Science Laboratory, Agricultural Research Station, College of Agriculture, Virginia State University, Petersburg, VA, USACooperate Extension, College of Agriculture, Virginia State University, Petersburg, VA, USACommon Research Laboratory, Agricultural Research Station, College of Agriculture, Virginia State University, Petersburg, VA, USAFood Chemistry and Nutrition Science Laboratory, Agricultural Research Station, College of Agriculture, Virginia State University, Petersburg, VA, USABackground: 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.https://foodandnutritionresearch.net/index.php/fnr/article/view/9126/15367lipid dropletsfatty acidsobesityglucose uptakeadipogenesislipogenesis
spellingShingle Haiwen Li
Ahmed Reza Rafie
Anwar Hamama
Rafat A. Siddiqui
Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes
Food & Nutrition Research
lipid droplets
fatty acids
obesity
glucose uptake
adipogenesis
lipogenesis
title Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes
title_full Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes
title_fullStr Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes
title_full_unstemmed Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes
title_short Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes
title_sort immature ginger reduces triglyceride accumulation by downregulating acyl coa carboxylase and phosphoenolpyruvate carboxykinase 1 genes in 3t3 l1 adipocytes
topic lipid droplets
fatty acids
obesity
glucose uptake
adipogenesis
lipogenesis
url https://foodandnutritionresearch.net/index.php/fnr/article/view/9126/15367
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AT ahmedrezarafie immaturegingerreducestriglycerideaccumulationbydownregulatingacylcoacarboxylaseandphosphoenolpyruvatecarboxykinase1genesin3t3l1adipocytes
AT anwarhamama immaturegingerreducestriglycerideaccumulationbydownregulatingacylcoacarboxylaseandphosphoenolpyruvatecarboxykinase1genesin3t3l1adipocytes
AT rafatasiddiqui immaturegingerreducestriglycerideaccumulationbydownregulatingacylcoacarboxylaseandphosphoenolpyruvatecarboxykinase1genesin3t3l1adipocytes