Lipid droplets hypertrophy: a crucial determining factor in insulin regulation by adipocytes

被引:25
作者
Sanjabi, Bahram [1 ,2 ]
Dashty, Monireh [3 ]
Ozcan, Behiye [4 ]
Akbarkhanzadeh, Vishtaseb [5 ]
Rahimi, Mehran [6 ]
Vinciguerra, Manlio [7 ,8 ]
van Rooij, Felix [9 ]
Al-Lahham, Saad [10 ]
Sheedfar, Fareeba [10 ,11 ]
van Kooten, Theo G. [12 ]
Spek, C. Arnold [13 ]
Rowshani, Ajda T. [14 ]
van der Want, Johannes [15 ]
Klaassen, Rene [16 ]
Sijbrands, Eric [9 ]
Peppelenbosch, Maikel P. [2 ]
Rezaee, Farhad [2 ,3 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands
[2] Univ Rotterdam, Erasmus Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands
[4] Erasmus MC, Dept Endocrinol, Rotterdam, Netherlands
[5] Univ Amsterdam, Med Univ Amsterdam, Inst Ctr 45, NL-1012 WX Amsterdam, Netherlands
[6] Univ Groningen, Univ Med Ctr Groningen, Fac Med Sci, Groningen, Netherlands
[7] UCL, Div Med, Inst Liver & Digest Hlth, London, England
[8] IRCCS Casa Sollievo Sofferenza, Gastroenterol Unit, San Giovanni Rotondo, Italy
[9] Erasmus MC, Dept Cardiovasc Genet, Metabolism, Rotterdam, Netherlands
[10] Univ Groningen, Univ Med Ctr Groningen, Dept Med Biol, Groningen, Netherlands
[11] Radboud Univ Nijmegen, Med Ctr, Dept Physiol, NL-6525 ED Nijmegen, Netherlands
[12] Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Engn, Groningen, Netherlands
[13] Univ Amsterdam, Acad Med Ctr, Dept Expt & Mol Med, NL-1012 WX Amsterdam, Netherlands
[14] Erasmus MC, Sect Nephrol & Transplantat, Dept Internal Med, Rotterdam, Netherlands
[15] Norwegian Univ Sci & Technol, Dept Lab Med Childrens & Womens Hlth, N-7034 Trondheim, Norway
[16] Maas City Hosp, Dept Surg Bariatr Surg, Rotterdam, Netherlands
关键词
INFLAMMATION; OBESITY; GLUCOSE; FAT; PREVENTION; CELLS; ADIPOGENESIS; MACROPHAGES; SENSITIVITY; METABOLISM;
D O I
10.1038/srep08816
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete insulin, which is biologically functional. Insulin concentrations and release are fat mass-and LDs-dependent respectively. Fat reduction mediated by bariatric surgery repairs obesity-associated T2D. The expression of genes, like PCSK1 (proinsulin conversion enzyme), GCG (Glucagon), GPLD1, CD38 and NNAT, involved in insulin regulation/release were differentially expressed in pancreas and adipose tissue (AT). INS (insulin) and GCG expression reduced in human AT-T2D as compared to AT-control, but remained unchanged in pancreas in either state. Insulin levels (mRNA/protein) were higher in AT derived from prediabetes BB rats with destructed pancreatic beta-cells and controls than pancreas derived from the same rats respectively. Insulin expression in 10 human primary cell types including adipocytes and macrophages is an evidence for extrapancreatic insulin-producing cells. The data suggest a crosstalk between AT and pancreas to fine-tune energy metabolic system or may minimize the metabolic damage during diabetes. This study opens new avenues towards T2D therapy with a great impact on public health.
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页数:12
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