Obesity- Associated Gallstone Complications: Investigating HMG-CoA Gene Expression and Spexin Biomarkers
Keywords:
Gallstone, Obesity, β-Hydroxyl β-Methyl glut aryl Co-A, Spexin, C-reactive protein, Lipid ProfileAbstract
Gallstone disease (GSD) is a prevalent and painful disorder characterized by the development of solid deposits in the gallbladder or bile ducts, including cholesterol, bile pigments, and calcium. While obesity is the main risk factor for GSD, the condition can also affect individuals who are not obese. This study examined the factors in obese and non-obese patients that may contribute to the formation and progression of gallstones, emphasizing the roles of β-Hydroxy β-Methylglutaryl Co-A gene expression and Spexin levels in driving inflammation.
The study involved 120 participants: 30 patients with symptomatic gallstones and obesity, 30 patients with symptomatic gallstones but no obesity, 30 obese patients without gallstones, and 30 healthy controls. Lipid profile levels (total cholesterol, triglycerides, HDL, LDL, and VLDL) were measured using an automatic Fuji film analyzer. Serum C-reactive protein (CRP) was quantified using an I-Chroma reader. Serum SPX levels were determined by enzyme-linked immunosorbent assay (ELISA), and HMG Co-A gene expression was analyzed using quantitative polymerase chain reaction (qPCR). Data were analyzed with SPSS version 28, with statistical significance set at P < 0.05.
The findings indicated an increase in lipid profile values and a decrease in HDL levels in all patient groups compared to controls, which was associated with heightened inflammation, as reflected by elevated CRP levels. Additionally, there were decreased SPX levels and a rise in HMG Co-A gene expression (P < 0.05).
In conclusion, the study suggests that the levels of SPX are negatively correlated with HMG Co-A gene expression, which may play a crucial role in triggering inflammation in gallstone patients, thus contributing to the progression of the disease, particularly in obese individuals.
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Ramaswamy, K., Killilea, D. W., Kapahi, P., Kahn, A. J., Chi, T., & Stoller, M. L. (2015). The elementome of calcium-based urinary stones and its role in urolithiasis. Nature Reviews Urology, 12(10), 543-557.
Ghai, C. L. (2012). A textbook of practical physiology. JP Medical Ltd.
Shabanzadeh, D. M. (2018). New determinants for gallstone disease. Dan Med J, 65(2), B5438.
Wang, D. Q. H., Neuschwander-Tetri, B. A., & Portincasa, P. (2012). The Biliary System, Colloquium Series on Integrated Systems Physiology: From Molecule to Function. Morgan & Claypool, 109-145.
Halldestam, I., Enell, E. L., Kullman, E., & Borch, K. (2004). Development of symptoms and complications in individuals with asymptomatic gallstones. Journal of British Surgery, 91(6), 734-738.
Ruhl, C. E., & Everhart, J. E. (2011). Gallstone disease is associated with increased mortality in the United States. Gastroenterology, 140(2), 508-516.
Thi Mong Diep Nguyen. (2020). Adiponectin: Role in Physiology and Pathophysiology. Int. J. Prev. Med. 11, 136.
Gill, T.; Hughes, R.; Tunidau-Schultz, J.; Nishida, C.; Gauden Galea and Cavalli-Sforza L. T. (2002). Obesity in the Pacific: Too Big To Ignore. Published with financial assistance from WHO. Regional Office, Manila, and the Government of Australia New Caledonia.
Mission Surgical Clinic. (2024). Understanding the Link Between Obesity and Gallbladder Disease. July 26. (888) 294-5296.
Gurbulak EK, Gurbulak B, Akgun IE, Duzkoylu Y, Battal M, Celayir MF, Demir U. (2015) Prediction of the grade of acute cholecystitis by plasma level of C-reactive protein. Iran Red Crescent Med J 17(4): e28091.
Andy Tran, Wenyuan He, Jim T.C. Chen, Denise D. Belsham. (2022). "Spexin: Its role, regulation, and therapeutic potential in the hypothalamus". Pharmacology & Therapeutics. Volume 233, May 2022, 108033
Wong MK, Sze KH, Chen T, et al. (2013). Gold-fish Spexin: solution structure and novel function as a satiety factor in feeding control. Am J Physiol Endocrinol Metab. Aug 1;305(3): E348-66.
Cheng-yuan Lin, Ling Zhao, Tao Huang, Lin Lu, Mahjabin Khan, Jie Liu, Linda L. D. Zhong, Zong-wei Cai, Bao-min Fan, Anderson O. L. Wong, and Zhao-Xiang Bian. (2018). "Spexin Acts as Novel Regulator for Bile Acid Synthesis". Frontiers in Physiology. April | Volume 9 | Article 378.
Lyu, Q., Yang, W., Li, Z., & Liang, X. (2022). "Spexin is a potential therapeutic target in inflammation and metabolic diseases". Current Pharmaceutical Design, 28(16), 1314-1322.
Shabbir, M., & Zeyad, A. (2019). The emerging role of adipokines in obesity-related diseases: Spexin and its impact on metabolic health. Journal of Clinical Endocrinology and Metabolism, 104(11), 4684-4695.
Behrooz M, Vaghef-Mehrabany E, Ostadrahimi A. (2020). Different Spexin level in obese vs normal-weight children and its relationship with obesity-related risk factors. Nutr Metab Cardiovasc Dis. Apr 12;30 (4):674-682.
Said MA, Nafeh NY, Abdallah HA. (2021) Spexin alleviates hypertension, hyperuricemia, dyslipidemia, and insulin resistance in high fructose diet-induced metabolic syndrome in rats via enhancing PPAR-ɣ and AMPK and inhibiting IL-6 and TNF-alpha. ARCH PHYSIOL BIOCHEM:1–6.
Ahlberg J, Angelin B, Einarsson K. (1981). Hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase activity and biliary lipid composition in man: relation to cholesterol gallstone disease and effects of cholic acid and chenodeoxycholic acid treatment. J Lipid Res, 22: 410-22.
Okunogbe et al., (2022) "Economic Impacts of Overweight and Obesity." BMJ Glob Health. 2022 Sep;7(9): e009773
Carol Barahona Ponce, Dominique Scherer, et al. (2021) "Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data". Hepatology. 2021 May;73(5):1783-1796
Aune D, Norat T, Vatten LJ. (2015)."Body mass index, abdominal fatness and the risk of gallbladder disease". Eur J Epidemiol. Sep;30(9):1009– 19.
Waleed H Albuali. (2014). Evaluation of oxidant-antioxidant status in overweight and morbidly obese Saudi children. World J Clin Pediatr. Feb 8;3(1):6-13.
Muhammad Sarwar Bhatti, Zamir Ahmad Akbri, Muhammad Shakoor. (2001) "Lipid profile in obesity". Journal of Ayub Medical College Abbottabad. January, 13(1):31-3
R.M. Manapurath, R. Hadaye, B. Gadapani. (2022) "Normal weight obesity: role of apoB and insulin Sensitivity in predicting future cardiovascular risk". Int J Prev Med, 13, p. 31
Aune D, Norat T, Vatten LJ. (2015). Body mass index, abdominal fatness, and the risk of gallbladder disease. Eur J Epidemiol. 30(9):1009–19
Hongliang Li & Congfeng Zhang. (2024). Association between the triglyceride-glucose index and gallstones: a cross-sectional study. Scientific Reports 17778.
Ruqaya S. Reda and Nawal Khinteel Jabbar. (2023). MicroRNA-122 as a Biomarker Associated with Inflammation in Patients Suffering from Metabolic Diseases. Applied Sciences, Information and Communication Technology. 978-0-7354-4715
Li Q, Wang Q, Xu W, Ma Y, Wang Q, Eatman D, You S, Zou J, Champion J, Zhao L, Cui Y, Li W, Deng Y, Ma L, Wu B, Wang G, Zhang X, Wang Q, Bayorh MA and Song Q (2020) C-Reactive Protein Causes Adult-Onset Obesity Through Chronic Inflammatory Mechanism. Front. Cell Dev. Biol. 8:18.
Ibraheem M. Rajab, Daniel Majerczyk, Margaret E. Olson, Jenna M. B. Addams, Mihee L. Choe, Matthew S. Nelson & Lawrence A. Potempa. (2020). "C-reactive protein in gallbladder diseases: diagnostic and therapeutic insights". Biophys Rep 6, 49–67
Lv, S. Y., Zhou, Y. C., Zhang, X. M., Chen, W. D. & Wang, Y. D. (2019). Emerging roles of NPQ/spexin in physiology and pathology. Front. Pharmacol. 10, 457
Mei Yu, Mengxian Ju, Penghua Fang, Zhenwen Zhang. (2022) "Emerging central and peripheral actions of spexin in feeding behavior, leptin resistance, and obesity".Biochemical Pharmacology. Volume 202, August, 115121
Zeng et. al. (2024). Spexin ameliorated obesity-related metabolic disorders by promoting white adipose browning mediated by the JAK2-STAT3 pathway. Nutrition & Metabolism. 21:22
Lau, J. M., et al. (2018). "Regulation of cholesterol metabolism in obesity: Role of HMG-CoA reductase." Journal of Lipid Research.
Xiao ZL, Chen Q, Amaral J, Biancani P, Jensen RT, Behar J. (1999). CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones. Am J Physiol. 276: G1401-7
Tushuizen, M. E., et al. (2006): "The impact of cholesterol metabolism and HMG-CoA reductase on the formation of gallstones in patients with metabolic syndrome." The Journal of Clinical Endocrinology & Metabolism.
B Angelin, L Backman, K Einarsson, L Eriksson, S Ewerth. (1982). Hepatic cholesterol metabolism in obesity: activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Lipid Res. Jul;23(5):770-3
Cheng-yuan Lin, Tao Huang, Ling Zhao, Linda L D Zhong, Wai Ching Lam, Bao-min Fan, Zhao-Xiang Bian. (2018). "Circulating Spexin Levels Negatively Correlate With Age, BMI, Fasting Glucose, and Triglycerides in Healthy Adult Women". J Endocr Soc. Apr 3;2(5):409–419
Locke A.E., Kahali B., Berndt S.I., Justice A.E., Pers T.H., Day F.R., Powell C., Vedantam S., Buchkovich M.L., Yang J., et al. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature. 518:197–206.
Schachter M. (2004). Chemical, pharmacokinetic and pharmacodynamic properties of statins: An update. Fundam. Clin. Pharmacol. 19:117–125.
Meng Y., Lv P., Ding G., Yu T., Liu Y., Shen Y., Hu X., Lin X., Tian S., Lv M., et al. (2015). High Maternal Serum Estradiol Levels Induce Dyslipidemia in Human Newborns via a Hepatic HMGCR Estrogen Response Element. Sci. Rep. 5:10086.
Belfiore, F., et al. (2017). HMGCR activity and triglyceride metabolism in metabolic disorders. Metabolism.
Benedetta Perrone, Paola Ruffo, Giuseppina Augimeri, Diego Sisci, Maria Stefania Sinicropi, Giovanni Tripepi, Corrado Mammì, Daniela Bonofiglio & Francesca Luisa Conforti. (2023). "Association between HMGCR, CRP, and CETP gene polymorphisms and metabolic/inflammatory serum profile in healthy adolescents". Journal of Translational Medicine volume 21, Article number: 718.
John R. Burnett, Lisa J. Wilcox, Dawn E. Telford, Sandra J. Kleinstiver, P. Hugh R. Barrett, Roger S. Newton, and Murray W. Huff. (1997). "Inhibition of HMG-CoA Reductase by Atorvastatin Decreases Both VLDL and LDL Apolipoprotein B Production in Miniature Pigs". Arteriosclerosis, Thrombosis, and Vascular Biology. Volume 17, Number 11.
A. Cánovas, R. Quintanilla, D. Gallardo, I. Díaz, J.L. Noguera, O. Ramírez, R.N. Pena. (2010). "Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme". Animal. Volume 4, Issue 2, Pages 224-233.
Otunola G., Oloyede O., Oladiji A., Afolayan A. (2014). "Selected spices and their combination modulate hypercholesterolemia-induced oxidative stress in experimental rats". Biol. Res. 47:5.
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