Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice.

Ahead of Print

Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101686284 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2509-2723 (Electronic) Linking ISSN: 25092723 NLM ISO Abbreviation: Geroscience Subsets: MEDLINE

Original Publication: Cham : Springer International Publishing, [2017]-

Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging - the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1 ^df gene mutation, these mice exhibit a deficiency in growth hormone (GH), prolactin, and TSH, alongside extremely low circulating IGF-1 levels. Intriguingly, while surgical removal of visceral fat (VFR) enhances insulin sensitivity in normal mice, it paradoxically increases insulin resistance in Ames dwarfs. This suggests an altered profile of factors produced in visceral fat in the absence of GH, indicating a unique interplay between adipose tissue function and hormonal influences in these models. Our aim was to analyze the gene expression related to lipid and glucose metabolism, insulin pathways, inflammation, thermoregulation, mitochondrial biogenesis, and epigenetic regulation in the visceral (perirenal and epididymal) adipose tissue of Ames dwarf and normal mice. Our findings reveal an upregulation in the expression of key genes such as Lpl, Adrβ3, Rstn, Foxo1, Foxo3a, Irs1, Cfd, Aldh2, Il6, Tnfα, Pgc1α, Ucp2, and Ezh2 in perirenal and Akt1, Foxo3a, PI3k, Ir, Acly, Il6, Ring1a, and Ring 1b in epididymal fat in df/df mice. These results suggest that the longevity phenotype in Ames dwarfs, which is determined by peripubertal GH/IGF-1 levels, may also involve epigenetic reprogramming of adipose tissue influenced by hormonal changes. The increased expression of genes involved in metabolic regulation, tumor suppression, mitochondrial biogenesis, and insulin pathways in Ames dwarf mice highlights potentially beneficial aspects of this model, opening new avenues for understanding the molecular underpinnings of longevity and aging.
(© 2024. The Author(s), under exclusive licence to American Aging Association.)

Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science. 2003;299:1346–51. (PMID: 1261029410.1126/science.1081447)
Everitt AV. The neuroendocrine system and aging. Gerontology. 1980;26:108–19. (PMID: 610131910.1159/000212403)
van den Beld AW, Kaufman JM, Zillikens MC, Lamberts SWJ, Egan JM, van der Lely AJ. The physiology of endocrine systems with ageing. Lancet Diabetes Endocrinol. 2018;6:647–58. (PMID: 30017799608922310.1016/S2213-8587(18)30026-3)
Barzilai N, Gabriely I, Atzmon G, Suh Y, Rothenberg D, Bergman A. Genetic studies reveal the role of the endocrine and metabolic systems in aging. J Clin Endocrinol Metab. 2010;95:4493–500. (PMID: 20926537305009610.1210/jc.2010-0859)
Bickel MA, Csik B, Gulej R, Ungvari A, Nyul-Toth A, Conley SM. Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis. Front Endocrinol (Lausanne). 2023;14:1087053. (PMID: 3675592210.3389/fendo.2023.1087053)
Gulej R, Nyul-Toth A, Csik B, Petersen B, Faakye J, Negri S, Chandragiri SS, Mukli P, Yabluchanskiy A, Conley S, Huffman DM, Csiszar A, Tarantini S, Ungvari Z. Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis: insights into neurovascular coupling and the impact of young blood factors. Geroscience. 2024;46:327–47. (PMID: 3812389010.1007/s11357-023-01039-2)
Zhang B, Lee DE, Trapp A, Tyshkovskiy A, Lu AT, Bareja A, Kerepesi C, McKay LK, Shindyapina AV, Dmitriev SE, Baht GS, Horvath S, Gladyshev VN, White JP. Multi-omic rejuvenation and life span extension on exposure to youthful circulation. Nat Aging. 2023;3:948–64. (PMID: 3750097310.1038/s43587-023-00451-9)
Yousefzadeh MJ, Wilkinson JE, Hughes B, Gadela N, Ladiges WC, Vo N, Niedernhofer LJ, Huffman DM, Robbins PD. Heterochronic parabiosis regulates the extent of cellular senescence in multiple tissues. Geroscience. 2020;42:951–61. (PMID: 32285290728699810.1007/s11357-020-00185-1)
Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014;20:659–63. (PMID: 24793238422443610.1038/nm.3569)
Kiss T, Tarantini S, Csipo T, Balasubramanian P, Nyul-Toth A, Yabluchanskiy A, Wren JD, Garman L, Huffman DM, Csiszar A, Ungvari Z. Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood. Geroscience. 2020;42:727–48. (PMID: 32172434720595410.1007/s11357-020-00180-6)
Kiss T, Nyul-Toth A, Gulej R, Tarantini S, Csipo T, Mukli P, Ungvari A, Balasubramanian P, Yabluchanskiy A, Benyo Z, Conley SM, Wren JD, Garman L, Huffman DM, Csiszar A, Ungvari Z. Old blood from heterochronic parabionts accelerates vascular aging in young mice: transcriptomic signature of pathologic smooth muscle remodeling. Geroscience. 2022;44:953–81. (PMID: 35124764913594410.1007/s11357-022-00519-1)
Zhao Y, Yue R. Aging adipose tissue, insulin resistance, and type 2 diabetes. Biogerontology. 2024;25:53–69. (PMID: 3772529410.1007/s10522-023-10067-6)
Stout MB, Justice JN, Nicklas BJ, Kirkland JL. Physiological aging: links among adipose tissue dysfunction, diabetes, and frailty. Physiology (Bethesda). 2017;32:9–19. (PMID: 27927801)
Miller KN, Burhans MS, Clark JP, Howell PR, Polewski MA, DeMuth TM, Eliceiri KW, Lindstrom MJ, Ntambi JM, Anderson RM. Aging and caloric restriction impact adipose tissue, adiponectin, and circulating lipids. Aging Cell. 2017;16:497–507. (PMID: 28156058541819810.1111/acel.12575)
Kavanagh K, Sherrill C, Ruggiero A, Block M, Vemuri R, Davis M, Olivier A. Biomarkers of senescence in non-human primate adipose depots relate to aging. Geroscience. 2021;43:343–52. (PMID: 3270540910.1007/s11357-020-00230-z)
Stout MB, Tchkonia T, Pirtskhalava T, Palmer AK, List EO, Berryman DE, Lubbers ER, Escande C, Spong A, Masternak MM, Oberg AL, LeBrasseur NK, Miller RA, Kopchick JJ, Bartke A, Kirkland JL. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging (Albany NY). 2014;6:575–86. (PMID: 2506377410.18632/aging.100681)
Wiesenborn DS, Menon V, Zhi X, Do A, Gesing A, Wang Z, Bartke A, Altomare DA, Masternak MM. The effect of calorie restriction on insulin signaling in skeletal muscle and adipose tissue of Ames dwarf mice. Aging (Albany NY). 2014;6:900–12. (PMID: 2541124110.18632/aging.100700)
Wang Z, Al-Regaiey KA, Masternak MM, Bartke A. Adipocytokines and lipid levels in Ames dwarf and calorie-restricted mice. J Gerontol A Biol Sci Med Sci. 2006;61:323–31. (PMID: 1661169710.1093/gerona/61.4.323)
Victoria B, Dhahbi JM, Nunez Lopez YO, Spinel L, Atamna H, Spindler SR, Masternak MM. Circulating microRNA signature of genotype-by-age interactions in the long-lived Ames dwarf mouse. Aging Cell. 2015;14:1055–66. (PMID: 26176567469347110.1111/acel.12373)
Masternak MM, Panici JA, Wang F, Wang Z, Spong A. The effects of growth hormone (GH) treatment on GH and insulin/IGF-1 signaling in long-lived Ames dwarf mice. J Gerontol A Biol Sci Med Sci. 2010;65:24–30. (PMID: 1990682210.1093/gerona/glp172)
Louis A, Bartke A, Masternak MM. Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice. J Gerontol A Biol Sci Med Sci. 2010;65:344–52. (PMID: 2020008810.1093/gerona/glq018)
Hill CM, Fang Y, Miquet JG, Sun LY, Masternak MM, Bartke A. Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure. Aging Cell. 2016;15:509–21. (PMID: 26990883485490610.1111/acel.12467)
Gesing A, Al-Regaiey KA, Bartke A, Masternak MM. Growth hormone abolishes beneficial effects of calorie restriction in long-lived Ames dwarf mice. Exp Gerontol. 2014;58:219–29. (PMID: 2515238810.1016/j.exger.2014.08.010)
Do A, Menon V, Zhi X, Gesing A, Wiesenborn DS, Spong A, Sun L, Bartke A, Masternak MM. Thyroxine modifies the effects of growth hormone in Ames dwarf mice. Aging (Albany NY). 2015;7:241–55. (PMID: 2593583810.18632/aging.100739)
Dhahbi J, Li X, Tran T, Masternak MM, Bartke A. Circulating blood leukocyte gene expression profiles: effects of the Ames dwarf mutation on pathways related to immunity and inflammation. Exp Gerontol. 2007;42:772–88. (PMID: 17611063204564210.1016/j.exger.2007.04.004)
Bates DJ, Li N, Liang R, Sarojini H, An J, Masternak MM, Bartke A, Wang E. MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. Aging Cell. 2010;9:1–18. (PMID: 1987814810.1111/j.1474-9726.2009.00529.x)
Csiszar A, Labinskyy N, Perez V, Recchia FA, Podlutsky A, Mukhopadhyay P, Losonczy G, Pacher P, Austad SN, Bartke A, Ungvari Z. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol. 2008;295:H1882–94. (PMID: 18757483261458810.1152/ajpheart.412.2008)
Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O’Connell SM, Gukovsky I, Carriere C, Ryan AK, Miller AP, Zuo L, Gleiberman AS, Andersen B, Beamer WG, Rosenfeld MG. Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature. 1996;384:327–33. (PMID: 893451510.1038/384327a0)
Andersen B, Pearse RV 2nd, Jenne K, Sornson M, Lin SC, Bartke A, Rosenfeld MG. The Ames dwarf gene is required for Pit-1 gene activation. Dev Biol. 1995;172:495–503. (PMID: 861296610.1006/dbio.1995.8040)
Hunter WS, Croson WB, Bartke A, Gentry MV, Meliska CJ. Low body temperature in long-lived Ames dwarf mice at rest and during stress. Physiol Behav. 1999;67:433–7. (PMID: 1049796310.1016/S0031-9384(99)00098-0)
Ikeno Y, Bronson RT, Hubbard GB, Lee S, Bartke A. Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci. 2003;58:291–6. (PMID: 1266369110.1093/gerona/58.4.B291)
Bartke A, Brown-Borg H. Life extension in the dwarf mouse. Curr Top Dev Biol. 2004;63:189–225. (PMID: 1553601710.1016/S0070-2153(04)63006-7)
Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996;384:33. (PMID: 890027210.1038/384033a0)
Noureddine S, Saccon T, Rudeski-Rohr T, Gesing A, Mason JB, Schneider A, Dhabhi J, Puig KL, Rakoczy S, Brown-Borg HM, Masternak MM. GH deficiency confers protective advantages against Alzheimer’s disease through rescued miRNA expression profile in APP/PS1 mice. Geroscience. 2022;44:2885–93. (PMID: 35900661976805310.1007/s11357-022-00633-0)
Masternak MM, Darcy J, Victoria B, Bartke A. Dwarf mice and aging. Prog Mol Biol Transl Sci. 2018;155:69–83. (PMID: 2965368310.1016/bs.pmbts.2017.12.002)
Panici JA, Harper JM, Miller RA, Bartke A, Spong A, Masternak MM. Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice. FASEB J. 2010;24:1–7.
Bartke A, Sun L, Fang Y, Hill C. Growth hormone actions during development influence adult phenotype and longevity. Exp Gerontol. 2016;86:22–7. (PMID: 26752217493073510.1016/j.exger.2015.12.011)
Nunes ADC, Weigl M, Schneider A, Noureddine S, Yu L, Lahde C, Saccon TD, Mitra K, Beltran E, Grillari J, Kirkland JL, Tchkonia T, Robbins PD, Masternak MM. miR-146a-5p modulates cellular senescence and apoptosis in visceral adipose tissue of long-lived Ames dwarf mice and in cultured pre-adipocytes. Geroscience. 2022;44:503–18. (PMID: 3482530410.1007/s11357-021-00490-3)
Menon V, Zhi X, Hossain T, Bartke A, Spong A, Gesing A, Masternak MM. The contribution of visceral fat to improved insulin signaling in Ames dwarf mice. Aging Cell. 2014;13:497–506. (PMID: 24690289403261810.1111/acel.12201)
Dominici FP, Hauck S, Argentino DP, Bartke A, Turyn D. Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice. J Endocrinol. 2002;173:81–94. (PMID: 1192738710.1677/joe.0.1730081)
Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes. 2002;51:2951–8. (PMID: 1235143210.2337/diabetes.51.10.2951)
Muzumdar R, Allison DB, Huffman DM, Ma X, Atzmon G, Einstein FH, Fishman S, Poduval AD, McVei T, Keith SW, Barzilai N. Visceral adipose tissue modulates mammalian longevity. Aging Cell. 2008;7:438–40. (PMID: 1836390210.1111/j.1474-9726.2008.00391.x)
Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Gerontol. 2009;44:625–33. (PMID: 19622391275367610.1016/j.exger.2009.07.003)
Zhang X, Wang Z, Li J, Gu D, Li S, Shen C, Song Z. Increased 4-hydroxynonenal formation contributes to obesity-related lipolytic activation in adipocytes. PLoS ONE. 2013;8: e70663. (PMID: 23940618373423810.1371/journal.pone.0070663)
Nadler ST, Stoehr JP, Schueler KL, Tanimoto G, Yandell BS, Attie AD. The expression of adipogenic genes is decreased in obesity and diabetes mellitus. Proc Natl Acad Sci U S A. 2000;97:11371–6. (PMID: 110273371720710.1073/pnas.97.21.11371)
Scarpulla RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta. 2011;1813:1269–78. (PMID: 2093302410.1016/j.bbamcr.2010.09.019)
Rowe GC, Arany Z. Genetic models of PGC-1 and glucose metabolism and homeostasis. Rev Endocr Metab Disord. 2014;15:21–9. (PMID: 24057597394376010.1007/s11154-013-9273-5)
Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab. 2006;3:333–41. (PMID: 1667929110.1016/j.cmet.2006.04.002)
Palikaras K, Lionaki E, Tavernarakis N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature. 2015;521:525–8. (PMID: 2589632310.1038/nature14300)
Lopez-Lluch G, Irusta PM, Navas P, de Cabo R. Mitochondrial biogenesis and healthy aging. Exp Gerontol. 2008;43:813–9. (PMID: 18662766256260610.1016/j.exger.2008.06.014)
Daskalaki I, Tavernarakis N. Mitochondrial biogenesis in organismal senescence and neurodegeneration. Mech Ageing Dev. 2020;191: 111345. (PMID: 3289160210.1016/j.mad.2020.111345)
Zhang C, Gao X, Li M, Yu X, Huang F, Wang Y, Yan Y, Zhang H, Shi Y, He X. The role of mitochondrial quality surveillance in skin aging: focus on mitochondrial dynamics, biogenesis and mitophagy. Ageing Res Rev. 2023;87: 101917. (PMID: 3697284210.1016/j.arr.2023.101917)
Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, Liu ZX, Dong J, Mustard KJ, Hawley SA, Befroy D, Pypaert M, Hardie DG, Young LH, Shulman GI. Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metab. 2007;5:151–6. (PMID: 17276357188596410.1016/j.cmet.2007.01.008)
Hara K, Tobe K, Okada T, Kadowaki H, Akanuma Y, Ito C, Kimura S, Kadowaki T. A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes. Diabetologia. 2002;45:740–3. (PMID: 1210775610.1007/s00125-002-0803-z)
Oropeza D, Jouvet N, Bouyakdan K, Perron G, Ringuette LJ, Philipson LH, Kiss RS, Poitout V, Alquier T, Estall JL. PGC-1 coactivators in beta-cells regulate lipid metabolism and are essential for insulin secretion coupled to fatty acids. Mol Metab. 2015;4:811–22. (PMID: 26629405463211410.1016/j.molmet.2015.08.001)
Hernandez-Alvarez MI, Thabit H, Burns N, Shah S, Brema I, Hatunic M, Finucane F, Liesa M, Chiellini C, Naon D, Zorzano A, Nolan JJ. Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1alpha/Mitofusin-2 regulatory pathway in response to physical activity. Diabetes Care. 2010;33:645–51. (PMID: 2003228110.2337/dc09-1305)
Hammarstedt A, Jansson PA, Wesslau C, Yang X, Smith U. Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance. Biochem Biophys Res Commun. 2003;301:578–82. (PMID: 1256590210.1016/S0006-291X(03)00014-7)
Gesing A, Bartke A, Wang F, Karbownik-Lewińska M, Masternak MM. Key regulators of mitochondrial biogenesis are increased in kidneys of growth hormone receptor knockout (GHRKO) mice. Cell Biochem Funct. 2011;29:459–67. (PMID: 21755522368247910.1002/cbf.1773)
Gesing A, Masternak MM, Wang F, Joseph A-M, Leeuwenburgh C, Westbrook R, Lewiński A, Karbownik-Lewińska M, Bartke A. Expression of key regulators of mitochondrial biogenesis in growth hormone receptor knockout (GHRKO) mice is enhanced but is not further improved by other potential life-extending interventions. J Gerontol A Biol Sci Med Sci. 2011;66A:1062–76. (PMID: 317256110.1093/gerona/glr080)
Gesing A, Masternak MM, Lewiński A, Karbownik-Lewińska M, Kopchick JJ, Bartke A. Decreased levels of proapoptotic factors and increased key regulators of mitochondrial biogenesis constitute new potential beneficial features of long-lived growth hormone receptor gene-disrupted mice. J Gerontol A Biol Sci Med Sci. 2013;68:639–51. (PMID: 2319718710.1093/gerona/gls231)
McDonald RB, Walker KM, Warman DB, Griffey SM, Warden CH, Ramsey JJ, Horwitz BA. Characterization of survival and phenotype throughout the life span in UCP2/UCP3 genetically altered mice. Exp Gerontol. 2008;43:1061–8. (PMID: 1885420810.1016/j.exger.2008.09.011)
Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91. (PMID: 767818310.1126/science.7678183)
Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab. 2002;87:2084–9. (PMID: 1199434510.1210/jcem.87.5.8450)
Matsubara T, Mita A, Minami K, Hosooka T, Kitazawa S, Takahashi K, Tamori Y, Yokoi N, Watanabe M, Matsuo E, Nishimura O, Seino S. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab. 2012;15:38–50. (PMID: 2222587510.1016/j.cmet.2011.12.002)
Maachi M, Pieroni L, Bruckert E, Jardel C, Fellahi S, Hainque B, Capeau J, Bastard JP. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord. 2004;28:993–7. (PMID: 1521136010.1038/sj.ijo.0802718)
Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS ONE. 2015;10: e0133494. (PMID: 26200663451172810.1371/journal.pone.0133494)
Bokov AF, Lindsey ML, Khodr C, Sabia MR, Richardson A. Long-lived ames dwarf mice are resistant to chemical stressors. J Gerontol A Biol Sci Med Sci. 2009;64:819–27. (PMID: 1941451010.1093/gerona/glp052)
Brown-Borg HM, Rakoczy SG, Sharma S, Bartke A. Long-living growth hormone receptor knockout mice: potential mechanisms of altered stress resistance. Exp Gerontol. 2009;44:10–9. (PMID: 1867533410.1016/j.exger.2008.07.002)
Harper JM, Salmon AB, Leiser SF, Galecki AT, Miller RA. Skin-derived fibroblasts from long-lived species are resistant to some, but not all, lethal stresses and to the mitochondrial inhibitor rotenone. Aging Cell. 2007;6:1–13. (PMID: 1715608410.1111/j.1474-9726.2006.00255.x)
Ungvari Z, Sosnowska D, Podlutsky A, Koncz P, Sonntag WE, Csiszar A. Free radical production, antioxidant capacity, and oxidative stress response signatures in fibroblasts from Lewis dwarf rats: effects of life span-extending peripubertal GH treatment. J Gerontol A Biol Sci Med Sci. 2011;66:501–10. (PMID: 2135024610.1093/gerona/glr004)
Wang H. Role of EZH2 in adipogenesis and obesity: current state of the art and implications — a review. Medicine (Baltimore). 2022;101: e30344. (PMID: 3608668710.1097/MD.0000000000030344)
Yiew NKH, Greenway C, Zarzour A, Ahmadieh S, Goo B, Kim D, Benson TW, Ogbi M, Tang YL, Chen W, Stepp D, Patel V, Hilton R, Lu XY, Hui DY, Kim HW, Weintraub NL. Enhancer of zeste homolog 2 (EZH2) regulates adipocyte lipid metabolism independent of adipogenic differentiation: Role of apolipoprotein E. J Biol Chem. 2019;294:8577–91. (PMID: 30971429654486210.1074/jbc.RA118.006871)
Dozmorov MG. Polycomb repressive complex 2 epigenomic signature defines age-associated hypermethylation and gene expression changes. Epigenetics. 2015;10:484–95. (PMID: 25880792462303110.1080/15592294.2015.1040619)
Sen P, Shah PP, Nativio R, Berger SL. Epigenetic mechanisms of longevity and aging. Cell. 2016;166:822–39. (PMID: 27518561582124910.1016/j.cell.2016.07.050)
Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Monch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 2007;21:525–30. (PMID: 17344414182089410.1101/gad.415507)
Fernandez S, Viola JM, Torres A, Wallace M, Trefely S, Zhao S, Affronti HC, Gengatharan JM, Guertin DA, Snyder NW, Metallo CM, Wellen KE. Adipocyte ACLY facilitates dietary carbohydrate handling to maintain metabolic homeostasis in females. Cell Rep. 2019;27(2772–2784): e6.
Fukuda H, Katsurada A, Iritani N. Effects of nutrients and hormones on gene expression of ATP citrate-lyase in rat liver. Eur J Biochem. 1992;209:217–22. (PMID: 139670010.1111/j.1432-1033.1992.tb17279.x)
Shimano H, Yahagi N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y, Shionoiri F, Iizuka Y, Ohashi K, Harada K, Gotoda T, Ishibashi S, Yamada N. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J Biol Chem. 1999;274:35832–9. (PMID: 1058546710.1074/jbc.274.50.35832)
Jiang L, Wang Q, Yu Y, Zhao F, Huang P, Zeng R, Qi RZ, Li W, Liu Y. Leptin contributes to the adaptive responses of mice to high-fat diet intake through suppressing the lipogenic pathway. PLoS ONE. 2009;4: e6884. (PMID: 19727392273122010.1371/journal.pone.0006884)
Kim K, Qiang L, Hayden MS, Sparling DP, Purcell NH, Pajvani UB. mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nat Commun. 2016;7:10255. (PMID: 26743335472987210.1038/ncomms10255)
Mathur A, Pandey VK, Kakkar P. PHLPP: a putative cellular target during insulin resistance and type 2 diabetes. J Endocrinol. 2017;233:R185–98. (PMID: 2842836310.1530/JOE-17-0081)
Hammoud SH, AlZaim I, Al-Dhaheri Y, Eid AH, El-Yazbi AF. Perirenal adipose tissue inflammation: novel insights linking metabolic dysfunction to renal diseases. Front Endocrinol (Lausanne). 2021;12: 707126. (PMID: 3440872610.3389/fendo.2021.707126)
Grigoras A, Balan RA, Caruntu ID, Giusca SE, Lozneanu L, Avadanei RE, Rusu A, Riscanu LA, Amalinei C. Perirenal adipose tissue—current knowledge and future opportunities. J Clin Med. 2021;10:1291. (PMID: 33800984800404910.3390/jcm10061291)
Sierra Rojas JX, Garcia-San Frutos M, Horrillo D, Lauzurica N, Oliveros E, Carrascosa JM, Fernandez-Agullo T, Ros M. Differential development of inflammation and insulin resistance in different adipose tissue depots along aging in Wistar rats: Effects of Caloric Restriction. J Gerontol A Biol Sci Med Sci. 2016;71:310–22. (PMID: 2641997710.1093/gerona/glv117)
Darcy J, Fang Y, McFadden S, Lynes MD, Leiria LO, Dreyfuss JM, Bussburg V, Tolstikov V, Greenwood B, Narain NR, Kiebish MA, Bartke A, Tseng YH. Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity. Geroscience. 2020;42:1527–46. (PMID: 32632845773293210.1007/s11357-020-00221-0)
Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, Hwang D, Martin-Montalvo A, Saavedra J, Ingles S, de Cabo R, Cohen P, Longo VD. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011;3:70ra13. (PMID: 21325617335762310.1126/scitranslmed.3001845)
Fazekas-Pongor V, Peterfi A, Major D, Szarvas Z, Fekete M, Tabak AG, Csiszar A, Sonntag WE, Austad SN, Ungvari ZI. Decreased lifespan in female “Munchkin” actors from the cast of the 1939 film version of The Wizard of Oz does not support the hypothesis linking hypopituitary dwarfism to longevity. Geroscience. 2022;44:2527–39. (PMID: 36334178976807510.1007/s11357-022-00680-7)

2016/21/B/NZ4/03192 Narodowe Centrum Nauki; TKP2021-NKTA-47 Hungarian Scientific Research Fund; RRF-2.3.1-21-2022-00003 Hungarian Scientific Research Fund

Keywords: Aging; Ames dwarf mice; Inflammation; Insulin pathway; Lipid and glucose metabolism; Mitochondrial biogenesis

Date Created: 20240322 Latest Revision: 20240322

20240323

10.1007/s11357-024-01131-1

38517641