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The role of ketone body‐utilizing enzyme, acetoacetyl‐CoA synthetase, in lipogenic tissue
Author(s) -
Hasegawa Shinya,
Yamasaki Masahiro,
Fukui Tetsuya
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.791.4
Subject(s) - gene knockdown , chemistry , neun , enzyme , adipocyte , biochemistry , medicine , adipose tissue , apoptosis , immunohistochemistry
Acetoacetyl‐CoA synthetase (AACS) is a ketone body‐utilizing enzyme for the synthesis of cholesterol and fatty acids and is highly expressed in the lipogenic tissues. In this study, we investigated the regulation of AACS in liver, adipocyte and neuron to clarify the physiological role of AACS. ChIP assay and knockdown experiments showed that AACS is mainly regulated by SREBP‐2 in the neuron and liver, and by C/EBP alpha in adipocytes. In 3T3‐L1 adipocytes, treatment with shRNA against AACS resulted in inhibition of lipid storage and reduction of adipocyte markers, such as C/EBP alpha and PPAR gamma. In the liver, knockdown of AACS using hydrodynamics method decreased total serum cholesterol. Moreover, suppression of AACS by shRNA in primary neurons caused decreases in the expression of MAP‐2 and NeuN, which are markers of neuronal differentiation, as well as synaptopodin, a marker of spine apparatus. These results suggest that ketone body utilization via AACS is an important reaction for lipogenic cellular function.