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CC BY-NC-ND 4.0 · Horm Metab Res 2024; 56(02): 159-166
DOI: 10.1055/a-2198-1132
Original Article: Endocrine Research

The Influence of Hyperglycemia on Liver Triglyceride Deposition in Partially Pancreatectomized Rats

Xiu-Ping Bai
1   Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan, China
,
Ting-Ting Li
1   Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan, China
,
Lai-Li Guo
1   Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan, China
,
Jing Wang
1   Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan, China
,
Feng Dong
2   Radiation Oncology, UTHSC at San Antonio, San Antonio, USA
› Author Affiliations Fundings International Science and Technology Cooperation and Exchange Program from the ShanXi Science and Technology Department in China — 202204041101008 ShanXi Science and Technology Department of China — 201901D111378 and 2014011044-3 Department of Resource and Social Security of ShanXi Province in China — 2016–97 ShanXi Scholarship Council of China — 2014–078Merck Diabetes Research Program of Chinese Medical Association — 13061040489
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Abstract

Nonalcoholic fatty liver disease and diabetes always coexist. The relationship of fatty liver and hyperglycemia is not clear. We studied the influence of hyperglycemia on triglyceride (TG) accumulation in the liver and explored its possible mechanisms. SD rats were divided into three groups: Group A (sham operation control), Group B (partially pancreatectomized rats), and Group C (partially pancreatectomized rats treated with insulin). At 4 weeks after surgery, pancreatic weights and liver TG contents were measured. Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed. The gene expression of sterol regulatory element-binding protein1c (SREBP-1c), carbohydrate regulatory element-binding protein (ChREBP), fatty acid synthase(FAS), carnitine palmitoyltransferase 1 (CPT-1), and fibroblast growth factor 21 (FGF21) was determined by real-time PCR. Compared with Group A, postprandial glucose increased significantly; the concentrations of insulin and C-peptides, pancreatic weights and serum FGF21 levels were decreased, liver TG was increased significantly in Group B, and insulin treatment improved these changes. Compared with Group A, the gene expressions of FGF21, CPT-1 and FAS in the liver were decreased in Group B (all p<0.05). Compared with Group B, the gene expressions of FGF21, FAS, ChREBP, SREBP-1c and CPT-1 in the liver in Group C were all increased significantly (p<0.05, respectively). Hyperglycemia induced by partial pancreatectomy could lead to increased liver TG. Insulin treatment could decrease glucose levels and improve fatty liver, and genes related to lipid metabolism may play a role in this process.

Key words

hyperglycemia - partial pancreatectomy - fatty liver - genes - lipid metabolism - metabolic syndrome


Publication History

Received: 13 August 2022

Accepted after revision: 17 October 2023

Article published online:
22 November 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol 2019; 7: 313-324
    CrossrefPubMedGoogle Scholar
  • 2 Hazlehurst JM, Woods C, Marjot T. et al. Non-alcoholic fatty liver disease and diabetes. Metabolism 2016; 65: 1096-1098
    CrossrefPubMedGoogle Scholar
  • 3 de Vries M, Westerink J, Kaasjager KHAH. et al. Prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes mellitus: a systematic review and meta-analysis. J Clin Endocrinol Metab 2020; 105: 3842-3853
    CrossrefPubMedGoogle Scholar
  • 4 Kummer S, Klee D, Kircheis G. et al. Screening for non-alcoholic fatty liver disease in children and adolescents with type 1 diabetes mellitus: a cross-sectional analysis. Eur J Pediatr 2017; 176: 529-536
    CrossrefPubMedGoogle Scholar
  • 5 Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology 2012; 142: 711-725.e6
    CrossrefPubMedGoogle Scholar
  • 6 Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism 2019; 92: 82-97
    CrossrefPubMedGoogle Scholar
  • 7 Samuel VT, Liu ZX, Qu X. et al. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 2004; 279: 32345-32353
    CrossrefPubMedGoogle Scholar
  • 8 Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010; 464: 1293-1300
    CrossrefPubMedGoogle Scholar
  • 9 Geisler CE, Renquist BJ. Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones. J Endocrinol 2017; 234: R1-R21
    CrossrefPubMedGoogle Scholar
  • 10 You M, Fischer M, Deeg MA. et al. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem 2002; 277: 29342-29347
    CrossrefPubMedGoogle Scholar
  • 11 Wang L, Zhang T, Wang L. et al. Fatty acid synthesis is critical for stem cell pluripotency via promoting mitochondrial fission. EMBO J 2017; 36: 1330-1347
    CrossrefPubMedGoogle Scholar
  • 12 Rui L. Energy metabolism in the liver. Compr Physiol 2014; 4: 177-197
    CrossrefPubMedGoogle Scholar
  • 13 Fisher FM, Estall JL, Adams AC. et al. Integrated regulation of hepatic metabolism by fibroblast growth factor 21 (FGF21) in vivo. Endocrinology 2011; 152: 2996-3004
    PubMedGoogle Scholar
  • 14 Tillman EJ, Rolph T. FGF21: An emerging therapeutic target for non-alcoholic steatohepatitis and related metabolic diseases. Front Endocrinol (Lausanne) 2020; 11: 601290
    CrossrefPubMedGoogle Scholar
  • 15 Rossetti L, Shulman GI, Zawalich W. et al. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J Clin Invest 1987; 80: 1037-1044
    CrossrefPubMedGoogle Scholar
  • 16 Yang W, Liu J, Shan Z. et al. Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol 2014; 2: 46-55
    CrossrefPubMedGoogle Scholar
  • 17 Cui A, Hu Z, Han Y. et al. Optimized analysis of in vivo and in vitro hepatic steatosis. J Vis Exp 2017; 121: 55178
    PubMedGoogle Scholar
  • 18 Siddiqui MT, Amin H, Garg R. et al. Medications in type-2 diabetics and their association with liver fibrosis. World J Gastroenterol 2020; 26: 3249-3259
    CrossrefPubMedGoogle Scholar
  • 19 Chon YE, Kim KJ, Jung KS. et al. The relationship between type 2 diabetes mellitus and non-alcoholic fatty liver disease measured by controlled attenuation parameter. Yonsei Med J 2016; 57: 885-892
    CrossrefPubMedGoogle Scholar
  • 20 Lonardo A, Lugari S, Ballestri S. et al. A round trip from nonalcoholic fatty liver disease to diabetes: molecular targets to the rescue?. Acta Diabetol 2019; 56: 385-396
    CrossrefPubMedGoogle Scholar
  • 21 Park J, Lee Y, Jung EH. et al. Glucosamine regulates hepatic lipid accumulation by sensing glucose levels or feeding states of normal and excess. Biochim Biophys Acta Mol Cell Biol Lipids 2020; 1865: 158764
    CrossrefPubMedGoogle Scholar
  • 22 Maersk M, Belza A, Stødkilde-Jørgensen H. et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 2012; 95: 283-289
    CrossrefPubMedGoogle Scholar
  • 23 Jensen T, Abdelmalek MF, Sullivan S. et al. Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. J Hepatol 2018; 68: 1063-1075
    CrossrefPubMedGoogle Scholar
  • 24 Schwimmer JB, Ugalde-Nicalo P, Welsh JA. et al. Effect of a low free sugar diet vs usual diet on nonalcoholic fatty liver disease in adolescent boys: a randomized clinical trial. JAMA 2019; 321: 256-265
    CrossrefPubMedGoogle Scholar
  • 25 Fletcher JA, Linden MA, Sheldon RD. et al. Fibroblast growth factor 21 and exercise-induced hepatic mitochondrial adaptations. Am J Physiol Gastrointest Liver Physiol 2016; 310: G832-G843
    CrossrefPubMedGoogle Scholar
  • 26 Linden AG, Li S, Choi HY. et al. Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. J Lipid Res 2018; 59: 475-487
    CrossrefPubMedGoogle Scholar
  • 27 Xu X, So JS, Park JG. et al. Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP. Semin Liver Dis 2013; 33: 301-311
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Dentin R, Girard J, Postic C. Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie 2005; 87: 81-86
    CrossrefPubMedGoogle Scholar
  • 29 Kliewer SA, Mangelsdorf DJ. A dozen years of discovery: insights into the physiology and pharmacology of FGF21. Cell Metab 2019; 29: 246-253
    CrossrefPubMedGoogle Scholar
  • 30 Samms RJ, Lewis JE, Norton L. et al. FGF21 is an insulin-dependent postprandial hormone in adult humans. J Clin Endocrinol Metab 2017; 102: 3806-3813
    CrossrefPubMedGoogle Scholar
  • 31 Fisher FM, Estall JL, Adams AC. et al. Integrated regulation of hepatic metabolism by fibroblast growth factor 21 (FGF21) in vivo. Endocrinology 2011; 152: 2996-3004
    CrossrefPubMedGoogle Scholar
  • 32 Miotto PM, Petrick HL, Holloway GP. Acute insulin deprivation results in altered mitochondrial substrate sensitivity conducive to greater fatty acid transport. Am J Physiol Endocrinol Metab 2020; 319: E345-E353
    CrossrefPubMedGoogle Scholar