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Archives of Physiology and Biochemistry
The Journal of Metabolic Diseases
Volume 125, 2019 - Issue 1
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Original Article

Obestatin protects and reverses nonalcoholic fatty liver disease and its associated insulin resistance in rats via inhibition of food intake, enhancing hepatic adiponectin signaling, and blocking ghrelin acylation

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Pages 64-78 | Received 11 Dec 2017, Accepted 03 Feb 2018, Published online: 10 Feb 2018

Refernces

  • Ahima, R.S., 2007. Insulin resistance: cause or consequence of nonalcoholic steatohepatitis. GastroentCerology, 132, 444–446.
  • Angulo, P., et al., 2004. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. Journal of hepatology, 41, 943–949.
  • Banks, A.S., et al., 2000. Activation of downstream signals by the long form of the leptin receptor. Journal of biological chemistry, 275, 4563–4572.
  • Bellone, S., et al., 2012. Acylated and unacylated ghrelin levels in normal weight and obese children: influence of puberty and relationship with insulin, leptin and adiponectin levels. Journal of endocrinological investigation 35, 191–197.
  • Blaak, E.E., 2003. Fatty acid metabolism in obesity and type 2 diabetes mellitus. Proceedings of the nutrition society, 62, 753–760.
  • Bresciani, E., et al., 2006. Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat. Journal of endocrinological investigation, 29, 2–4.
  • Brunt, E.M., 2004. Nonalcoholic steatohepatitis. Seminars in liver disease, 24, 3–20.
  • Buettner, R., et al., 2006. Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. Journal of molecular endocrinology, 36, 485–501.
  • Chabrolle, C., Tosca, L., and Dupont, J., 2007. Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction (Cambridge, England), 133, 719–731.
  • Chalasani, N., et al., 2003. Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis. American journal of gastroenterology, 98, 2771–2776.
  • Charlton, M., 2007. Noninvasive indices of fibrosis in NAFLD: starting to think about a three-hit (at least) phenomenon. American journal of gastroenterology, 102, 409–411.
  • Chartrel, N., et al., 2007. Comment on “obestatin”, a peptide encoded by the Ghrelin gene, opposes Ghrelin’s effects on food intake. Science, 80, 315–766.
  • Cohen, B.N.D. and Rubinstein, M., 1996. Modulation of insulin activities by leptin. Science (New York, N.Y.), 274, 1185–1188.
  • De Luca, C. and Olefsky, J.M., 2008. Inflammation and insulin resistance. FEBS Letters, 582, 97–105.
  • Delhanty, P.J., et al., 2010. Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice. PLoS One, 5, e11749.
  • Eman, F.K., Ghada, A.A., and Dalia, G.M., 2017. Resveratrol improves high fat diet-induced fatty liver and insulin resistance by concomitant inhibiting proteolytic cleavage of sterol binding elements –binding proteins, free fatty acid oxidation, and intestinal triglyceride absorption. Canadian journal of physiology and pharmacology, 4, 1–13.
  • Estep, M., et al., 2011. Association of obestatin, ghrelin, and inflammatory cytokines in obese patients with non-alcoholic fatty liver disease. Obesity surgery, 21, 1750–1757.
  • Folch, J., Lees, M., and Sobane, S., 1957. A simple method for isolation and purification of total lipid from animal tissues. Journal of biological chemistry, 226, 497–509.
  • Fraulob, J.C., et al., 2010. A mouse model of metabolic syndrome: insulin resistance, fatty liver and Non-Alcoholic Fatty Pancreas Disease (NAFPD) in C57BL/6 mice fed a high fat diet. Journal of clinical biochemistry and nutrition, 46, 212–223.
  • Gauna, C., et al., 2004. Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity. Journal of clinical endocrinology and metabolism, 89, 5035–5042.
  • Gauna, C., et al., 2005. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. Journal of clinical endocrinology and metabolism, 90, 1055–1060.
  • Gauna, C., et al., 2007. Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions. American journal of physiology- endocrinology and metabolism, 293, E697–E704.
  • González, C.R., et al., 2008. Influence of chronic undernutrition and leptin on GOAT mRNA levels in rat stomach mucosa. Journal of molecular endocrinology, 41, 415–421.
  • Gourcerol, G., et al., 2006. Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents. Peptides, 27, 2811–2819.
  • Granata, R., et al., 2012. Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation. FASEB journal : official publication of the federation of American societies for experimental biology, 26, 3393–3411.
  • Granata, R., et al., 2008. Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function. Diabetes, 57, 967–979.
  • Granata, R., et al., 2010. Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. Journal of molecular endocrinology, 45, 9–17.
  • Green, B.D., Irwin, N., and Flatt, P.R., 2007. Direct and indirect effects of obestatin peptides on food intake and the regulation of glucose homeostasis and insulin secretion in mice. Peptides, 28, 981–987.
  • Gutierrez-Grobe, Y., et al., 2010. High ghrelin and obestatin levels and low risk of developing fatty liver. Annals of hepatology, 9, 52–57.
  • Hosoda, H., et al., 2004. Optimum collection and storage conditions for ghrelin measurements: octanoyl modification of ghrelin is rapidly hydrolyzed to desacyl ghrelin in blood samples. Clinical chemistry, 50, 1077.
  • Jaeschke, H. and McCuskey, R.S., 2004. The importance of leptin in mice and man. Journal of hepatology, 40, 359–361.
  • Javor, E.D., et al., 2005. Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. Hepatology, 41, 753–760.
  • Kelley, D.E., et al., 2003. Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. American journal of physiology- endocrinology and metabolism, 285, E906–E916.
  • Kołodziejski, P.A., et al., 2017. Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function. Endocrine, 56, 538–550.
  • Li, Y., et al., 2013. Impairment of reproductive function in a male rat model of non-alcoholic fatty liver disease and beneficial effect of N-3 fatty acid supplementation. Toxicology letters, 222, 224–232.
  • Lieber, C.S., et al., 2004. Model of nonalcoholic steatohepatitis. American journal of clinical nutrition, 79, 502–509.
  • Lutchman, G., et al., 2006. Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: relationship to histological improvement. Clinical gastroenterology and hepatology, 4, 1048–1052.
  • Machado, M. and Cortez, P.H., 2005. Non-alcoholic fatty liver disease and insulin resistance. European journal of gastroenterology & hepatology, 17, 823–836.
  • Marchesini, G., et al., 2003. Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance. Journal of clinical endocrinology and metabolism, 88, 5674–5679.
  • Mather, K., 2009. Surrogate measures of insulin resistance: of rats, mice, and men. American journal of physiology- endocrinology and metabolism, 296, E398–E399.
  • Mehta, K., et al., 2002. Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. Nutrition Reviews, 60, 289–293.
  • Mendez-Sanchez, N., et al., 2005. Adiponectin as a protective factor in hepatic steatosis. World journal of gastroenterology, 11, 1737–1741.
  • Michael, E., et al., 2010. Serum obestatin concentrations in non-alcoholic fatty liver disease (NAFLD) with fibrosis. Gastroenterology, 38, S802.
  • Musso, G., et al., 2005. Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology , 42, 1175–1183.
  • Nakajima, K., 2012. Multidisciplinary pharmacotherapeutic options for nonalcoholic fatty liver disease. International journal of hepatology, 2012, 950693.
  • Nishi, Y., et al., 2005. Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin. Endocrinology, 146, 2255–2264.
  • Polyzos, S.A., et al., 2010. The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease. Diabetes, obesity & metabolism, 12, 365–383.
  • Polyzos, S.A., et al., 2016. Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia, 59, 30–43.
  • Rector, R.S., et al., 2008. Non-alcoholic fatty liver disease and the metabolic syndrome: an update. World journal of gastroenterology, 14, 185–192.
  • Ren, A.J., et al., 2009. Obestatin, obesity and diabetes. Peptides, 30, 439–444.
  • Rodríguez, A., et al., 2009. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. International journal of obesity 33, 541–552.
  • Rodríguez, A., et al., 2012. The ghrelin o-acetyltransferase-ghrelin system reduces TNF-α and autophagy in human visceral adipocytes. Diabetologia, 55, 3038–3050.
  • Sasidharan, S., et al., 2014. Ameliorative potential of tamarindus indica on high fat diet induced nonalcoholic fatty liver disease in rats. Scientific world journal, 2014, 507197.
  • Smolinski, D.J., et al., 2007. Additional nuclei and NOR activity during meiotic prophase 1in Irch(Larix decidua Mill). Protoplasm, 232, 109–120.
  • St-Pierre, D.H., et al., 2007. Association of acylated and nonacylated ghrelin with insulin sensitivity in overweight and obese postmenopausal women. Journal of clinical endocrinology and metabolism, 92, 264–269.
  • Svegliati-Baroni, G., et al., 2006. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-α and n-3 polyunsaturated fatty acid treatment on liver injury. The American journal of pathology, 169, 846–860.
  • Tsochatzis, E., Papatheodoridis, G.V., and Archimandritis, A.J., 2006. The evolving role of leptin and adiponectin in chronic liver diseases. The American journal of gastroenterology, 101, 2629–2640.
  • Van der Lely, A.J., et al., 2004. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocrine reviews, 25, 426–457.
  • Vuguin, P., et al., 2004. Hepatic insulin resistance precedes the development of diabetes in a model of intrauterine growth retardation. Diabetes, 53, 2617–6722.
  • Wang, Y.U., et al., 2009. Protective roles of adiponectin in obesity related fatty liver diseases: mechanisms and therapeutic implications. Arquivos brasileiros de endocrinologia & metabologia, 53, 201–212.
  • Wang, W., et al., 2013. Simvastatin ameliorates liver fibrosis via mediating nitric oxide synthase in rats with non-alcoholic steatohepatitis-related liver. PloS One, 8, e76538.
  • Weyer, C., et al., 2001. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. Journal of clinical endocrinology and metabolism, 86, 1930–1935.
  • Wiedmer, P., et al., 2007. Ghrelin, obesity and diabetes. Nature clinical practice endocrinology & metabolism, 3, 705–712.
  • Wulster-Radcliffe, M.C., et al., 2004. Adiponectin differentially regulates cytokines in porcine macrophages. Biochemical and biophysical research communications, 316, 924–929.
  • Yamanaka, O., et al., 2006. Interleukin-7 modulates extracellular matrix production and TGF-beta signaling in cultured human subconjunctival fibroblasts. Current eye research, 31, 491–499.
  • Yokota, T., et al., 2002. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood, 96, 1723–1732.
  • Zhang, J.V., et al., 2005. Obestatin, a peptide encoded by the Ghrelin gene, opposes ghrelin's effects on food intake. Science , 310, 996–999.
  • Zizzari, P., et al., 2007. Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents. Endocrinology, 148, 1648–1653.

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