Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats
Obesity has been linked to metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity causes a decrease in growth hormone (GH) levels and an increase in insulin levels. Long-term GH treatment increased lipolytic activity as opposed to decreasing insulin sensitivity....
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MDPI AG
2023-03-01
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| author | Sutharinee Likitnukul Sumpun Thammacharoen Orada Sriwatananukulkit Chanathip Duangtha Ruedee Hemstapat Chotchanit Sunrat Supachoke Mangmool Darawan Pinthong |
| author_facet | Sutharinee Likitnukul Sumpun Thammacharoen Orada Sriwatananukulkit Chanathip Duangtha Ruedee Hemstapat Chotchanit Sunrat Supachoke Mangmool Darawan Pinthong |
| author_sort | Sutharinee Likitnukul |
| collection | DOAJ |
| description | Obesity has been linked to metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity causes a decrease in growth hormone (GH) levels and an increase in insulin levels. Long-term GH treatment increased lipolytic activity as opposed to decreasing insulin sensitivity. Nonetheless, it is possible that short-term GH administration had no impact on insulin sensitivity. In this study, the effect of short-term GH administration on liver lipid metabolism and the effector molecules of GH and insulin receptors were investigated in diet-induced obesity (DIO) rats. Recombinant human GH (1 mg/kg) was then administered for 3 days. Livers were collected to determine the hepatic mRNA expression and protein levels involved in lipid metabolism. The expression of GH and insulin receptor effector proteins was investigated. In DIO rats, short-term GH administration significantly reduced hepatic fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) mRNA expression while increasing carnitine palmitoyltransferase 1A (CPT1A) mRNA expression. Short-term GH administration reduced hepatic FAS protein levels and downregulated gene transcription of hepatic fatty acid uptake and lipogenesis, while increasing fatty acid oxidation in DIO rats. DIO rats had lower hepatic JAK2 protein levels but higher IRS-1 levels than control rats due to hyperinsulinemia. Our findings suggest that short-term GH supplementation improves liver lipid metabolism and may slow the progression of NAFLD, where GH acts as the transcriptional regulator of related genes. |
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| language | English |
| last_indexed | 2024-03-11T05:12:58Z |
| publishDate | 2023-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-53d387e76cbb4e01b0b7cd18e9a0467d2023-11-17T18:25:49ZengMDPI AGBiomedicines2227-90592023-03-01114105010.3390/biomedicines11041050Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese RatsSutharinee Likitnukul0Sumpun Thammacharoen1Orada Sriwatananukulkit2Chanathip Duangtha3Ruedee Hemstapat4Chotchanit Sunrat5Supachoke Mangmool6Darawan Pinthong7Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDepartment of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandObesity has been linked to metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity causes a decrease in growth hormone (GH) levels and an increase in insulin levels. Long-term GH treatment increased lipolytic activity as opposed to decreasing insulin sensitivity. Nonetheless, it is possible that short-term GH administration had no impact on insulin sensitivity. In this study, the effect of short-term GH administration on liver lipid metabolism and the effector molecules of GH and insulin receptors were investigated in diet-induced obesity (DIO) rats. Recombinant human GH (1 mg/kg) was then administered for 3 days. Livers were collected to determine the hepatic mRNA expression and protein levels involved in lipid metabolism. The expression of GH and insulin receptor effector proteins was investigated. In DIO rats, short-term GH administration significantly reduced hepatic fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) mRNA expression while increasing carnitine palmitoyltransferase 1A (CPT1A) mRNA expression. Short-term GH administration reduced hepatic FAS protein levels and downregulated gene transcription of hepatic fatty acid uptake and lipogenesis, while increasing fatty acid oxidation in DIO rats. DIO rats had lower hepatic JAK2 protein levels but higher IRS-1 levels than control rats due to hyperinsulinemia. Our findings suggest that short-term GH supplementation improves liver lipid metabolism and may slow the progression of NAFLD, where GH acts as the transcriptional regulator of related genes.https://www.mdpi.com/2227-9059/11/4/1050GHDIO ratshepatic lipid metabolismNAFLDinsulin resistance |
| spellingShingle | Sutharinee Likitnukul Sumpun Thammacharoen Orada Sriwatananukulkit Chanathip Duangtha Ruedee Hemstapat Chotchanit Sunrat Supachoke Mangmool Darawan Pinthong Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats Biomedicines GH DIO rats hepatic lipid metabolism NAFLD insulin resistance |
| title | Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats |
| title_full | Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats |
| title_fullStr | Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats |
| title_full_unstemmed | Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats |
| title_short | Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats |
| title_sort | short term growth hormone administration mediates hepatic fatty acid uptake and de novo lipogenesis gene expression in obese rats |
| topic | GH DIO rats hepatic lipid metabolism NAFLD insulin resistance |
| url | https://www.mdpi.com/2227-9059/11/4/1050 |
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