REGULATORY ROLE OF ORNITHINE DECARBOXYLASE IN ADIPOGENESIS
DOI:
https://doi.org/10.32471/oncology.2663-7928.t-22-3-2020-g.9072Keywords:
adipocytes, adipogenesis, adipose tissue, glucose metabolism, neoplastic transformation, ornithine-decarboxylase, polyamines, spermineAbstract
The aim of this review is to summarize the contemporary data on the relationship between the activity of ornithine decarboxylase (ODC), polyamine (PA) metabolism and lipid metabolism in physiological and pathological conditions. ODC catalyzes the rate-limiting stage of polyamines biosynthesis, which are involved in many processes crucial for cell growth, division and differentiation. The role of ODC in neoplastic transformation and the involvement of ODC and polyamines in the proliferation and differentiation processes are analyzed. There is demonstrated the participation of ODC and polyamines in the regulation of quantitative and qualitative characteristics of the white adipose tissue cellular composition and the ratio of white and beige adipocytes. The impact of ODC activity and polyamine metabolism on lipid metabolism in adipocytes and regulation of adipose tissue mass is discussed. The inhibition of ODC activity prevents the differentiation of 3T3-L1 fibroblasts into adipocytes. Existing data suggest that the acceleration of the metabolic flow of polyamines due to the activation of spermidine/spermine-N1-acetyltransferase leads to a decrease in energy reserves in the cell; furthermore, its decline results in an increase in intracellular concentrations of neutral fats. Polyamines themselves, like a number of hormones, can affect lipid metabolism. The regulatory role of ODC in adipogenesis appears to be important for a growing number of metabolic diseases, insulin resistance, type 2 diabetes, atherosclerosis and cancer.
References
Brooks HB, Phillips MA. Characterization of the reaction mechanism for Trypanosoma brucei ornithine decarboxylase by multiwavelength stopped-flow spectroscopy. Biochemistry 1997; 36 (49): 15147–15155.
Jackson LK, Brooks HB, Osterman AL, et al. Altering the reaction specificity of eukaryotic ornithine decarboxylase. Biochemistry 2000; 39 (37): 11247–11257.
Pegg AE. Regulation of ornithine decarboxylase. J Biol Chem 2006; 281 (21): 14529–14532.
Raboni S, Spyrakis F, Campanini B, et al. Pyridoxal 5-phosphate-dependent enzymes: catalysis, conformation, and genomics. Comprehensive Natural Products II: Chemistry and Biology 2010; 7: 273–315.
Shantz LM, Guo Y, Sawicki JA, et al. Overexpression of a dominant-negative ornithine decarboxylase in mouse skin: effect on enzyme activity and papilloma formation. Carcinogenesis 2002; 23 (4): 657–664.
Coffino P. Regulation of cellular polyamines by antizyme. Nat Rev Mol cell Biol 2001; 2 (3): 188–194.
Murakami Y, Matsufuji S, Hayashi S, et al. Degradation of ornithine decarboxylase by the 26S proteasome. Biochem Biophys Res Commun 2000; 267 (1): 1–6.
Zhang M, Pickart CM, Coffino P. Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate. EMBO J 2003; 22 (7): 1488–1496.
Agha M, Agha R. The rising prevalence of obesity: part A: impact on public health. Int J surgery Oncol 2017; 2 (7): e17.
Bhupathiraju SN, Hu FB. Epidemiology of obesity and diabetes and their cardiovascular complications. Circ Res 2016; 118 (11): 1723–1735.
Pearson-Stuttard J, Zhou B, Kontis V, et al. Retracted: Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment. The Lancet Diabetes & Endocrinology 2018; 6 (2): 95–104.
Jamdar SC, Osborne LJ. Glycerolipid biosynthesis in rat adipose tissue: II. Effects of polyamines on Mg2+-dependent phosphatidate phosphohydrolase. Biochim Biophys Acta (BBA)-Lipids Lipid Metab 1983; 752 (1): 79–88.
Lockwood DH, East LE. Studies of the insulin-like actions of polyamines on lipid and glucose metabolism in adipose tissue cells. J Biol Chem 1974; 249: (24) 7717–7722.
Brenner S, Bercovich Z, Feiler Y, et al. Dual regulatory role of polyamines in adipogenesis. J Biol Chem 2015; 290 (45): 27384–27392.
Sadasivan SK, Vasamsetti B, Singh J, et al. Exogenous administration of spermine improves glucose utilization and decreases bodyweight in mice. Eur J Pharmacol 2014; 729: 94–99.
Gao M, Zhao W, Li C, et al. Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid metabolism via AMPK. Biochem Biophys Res Commun 2018; 505 (1): 93–98.
Jamdar SC, Cao WF, Samaniego E. Relationship between adipose polyamine concentrations and triacylglycerol synthetic enzymes in lean and obese Zucker rats. Enzym Protein 1996; 49: 222–230.
Böhm A, Halama A, Meile T, et al. Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals. PLoS One 2014; 9 (4): e93148.
Codoñer-Franch P, Tavárez-Alonso S, Murria-Estal R, et al. Polyamines are increased in obese children and are related to markers of oxidative/nitrosative stress and angiogenesis. J Clin Endocrinol Metab 2011; 96 (9): 2821–2825.
Vuohelainen S, Pirinen E, Cerrada-Gimenez M, et al. Spermidine is indispensable in differentiation of 3T3-L1 fibroblasts to adipocytes. J Cell Mol Med 2010; 14 (6b): 1683–1692.
Leon KE, Fruin AM, Nowotarski SL, et al. The regulation of triglyceride storage by ornithine decarboxylase (Odc1) in Drosophila. Biochem Biophys Res Commun 2020; 523 (2): 429–433.
Erwin BG, Bethell DR, Pegg AE. Role of polyamines in differentiation of 3T3-L1 fibroblasts into adipocytes. Am J Physiol Physiol 1984; 246 (3): C293–C300.
Shelepov VP, Chekulaev VA, Pasha-Zade GR. Effect of putrescine on carbohydrate and lipid metabolism in rats. Biomed Sci 1990; 1 (6): 591–596.
Ushmorov A, Hack V, Dröge W. Differential reconstitution of mitochondrial respiratory chain activity and plasma redox state by cysteine and ornithine in a model of cancer cachexia. Cancer Res 1999; 59 (14): 3527–3534.
Russell D, Snyder SH. Amine synthesis in rapidly growing tissues: ornithine decarboxylase activity in regenerating rat liver, chick embryo, and various tumors. Proc Natl Acad Sci USA 1968; 60 (4): 1420.
Cervelli M, Pietropaoli S, Signore F, et al. Polyamines metabolism and breast cancer: state of the art and perspectives. Breast Cancer Res Treat 2014; 148 (2): 233–248.
Gupta S, Ahmad N, Marengo SR, et al. Chemoprevention of prostate carcinogenesis by α-difluoromethylornithine in TRAMP mice. Cancer Res 2000; 60 (18): 5125–5133.
Gilmour SK. Polyamines and nonmelanoma skin cancer. Toxicol Appl Pharmacol 2007; 224 (3): 249–256.
Gerner EW, Bruckheimer E, Cohen A. Cancer pharmacoprevention: Targeting polyamine metabolism to manage risk factors for colon cancer. J Biol Chem 2018; 293 (48): 18770–18778.
Gerner EW, Meyskens FL. Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 2004; 4 (10): 781–792.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100 (1): 57–70.
Ahmad N, Gilliam AC, Katiyar SK, et al. A definitive role of ornithine decarboxylase in photocarcinogenesis. Am J Pathol 2001; 159 (3): 885–892.
Mohan RR, Challa A, Gupta S, et al. Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans. Clin Cancer Res 1999; 5 (1): 143–147.
Shantz LM, Levin VA. Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential. Amino Acids 2007; 33 (2): 213–223.
George K, Iacobucci A, Uitto J, et al. Identification of an X-linked locus modifying mouse skin tumor susceptibility. Mol Carcinog Publ Coop with Univ Texas MD Anderson Cancer Cent 2005; 44 (3): 212–218.
Hayes CS, DeFeo K, Lan L, et al. Elevated levels of ornithine decarboxylase cooperate with Raf/ERK activation to convert normal keratinocytes into invasive malignant cells. Oncogene 2006; 25 (10): 1543–1553.
Feith DJ, Origanti S, Shoop PL, et al. Tumor suppressor activity of ODC antizyme in MEK-driven skin tumorigenesis. Carcinogenesis 2006; 27: 1090–1098.
Feith DJ, Shantz LM, Pegg AE. Targeted antizyme expression in the skin of transgenic mice reduces tumor promoter induction of ornithine decarboxylase and decreases sensitivity to chemical carcinogenesis. Cancer Res 2001; 61 (16): 6073–6081.
Tang X, Kim AL, Feith DJ, et al. Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/–mice. J Clin Invest 2004; 113 (6): 867–875.
Giardiello FM, Hamilton SR, Hylind LM, et al. Ornithine decarboxylase and polyamines in familial adenomatous polyposis. Cancer Res 1997; 57 (2): 199–201.41. Luk GD, Baylin SB. Ornithine decarboxylase as a biologic marker in familial colonic polyposis. N Engl J Med 1984; 311 (2): 80–83.
