Modulation of polyamine metabolic flux in adipose tissue alters the accumulation of body fat by affecting glucose homeostasis.
Modulation of polyamine metabolic flux in adipose tissue alters the accumulation of body fat by affecting glucose homeostasis.
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DOI：
10.1007/s00726-013-1548-3
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发表时间：
2014-03
期刊：
影响因子：
3.5
通讯作者：
Merali, Salim
中科院分区：
文献类型：
--
作者：
Liu, Chunli;Perez-Leal, Oscar;Barrero, Carlos;Zahedi, Kamyar;Soleimani, Manoocher;Porter, Carl;Merali, Salim
The continued rise in obesity despite public education, awareness and policies indicates the need for mechanism-based therapeutic approaches to help control the disease. Our data, in conjunction with other studies, suggest an unexpected role for the polyamine catabolic enzyme spermidine/spermine-N1-acetyltransferase (SSAT) in fat homeostasis. Our previous studies showed that deletion of SSAT greatly exaggerates weight gain and that the transgenic overexpression suppresses weight gain in mice on a high-fat diet. This discovery is substantial but the underlying molecular linkages are only vaguely understood. Here, we used a comprehensive systems biology approach, on white adipose tissue (WAT), to discover that the partition of acetyl-CoA towards polyamine catabolism alters glucose homeostasis and hence, fat accumulation. Comparative proteomics and antibody-based expression studies of WAT in SSAT knockout, wild type and transgenic mice identified nine proteins with an increasing gradient across the genotypes, all of which correlate with acetyl-CoA consumption in polyamine acetylation. Adipose-specific SSAT knockout mice and global SSAT knockout mice on a high-fat diet exhibited similar growth curves and proteomic patterns in their WAT, confirming that attenuated consumption of acetyl-CoA in acetylation of polyamines in adipose tissue drives the obese phenotype of these mice. Analysis of protein expression indicated that the identified changes in the levels of proteins regulating acetyl-CoA consumption occur via the AMP-activated protein kinase pathway. Together, our data suggest that differential expression of SSAT markedly alters acetyl-CoA levels, which in turn trigger a global shift in glucose metabolism in adipose tissue, thus affecting the accumulation of body fat.
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影响因子：
4.4
作者：
Duan, Xunbao;Kelsen, Steven G.;Merali, Salim
通讯作者：
Merali, Salim
影响因子：
8.4
作者：
Antoniewicz, Maciek R.;Kraynie, David F.;Stephanopoulos, Gregory
通讯作者：
Stephanopoulos, Gregory
影响因子：
--
作者：
KLAUNIG, JE;GOLDBLATT, PJ;TRUMP, BF
通讯作者：
TRUMP, BF
影响因子：
64.8
作者：
Minokoshi, Y;Kim, YB;Kahn, BB
通讯作者：
Kahn, BB
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
Evans, RM