Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats
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Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats. / Wu, Kay Li Hui; Liu, Wen Chung; Wu, Chih Wei; Fu, Mu Hui; Huang, Hsiu Mei; Tain, You Lin; Liang, Chih Kuang; Hung, Chun Ying; Chen, I. Chun; Hung, Pi Lien; Lin, Yu Ju; Hirase, Hajime.
In: Journal of Nutritional Biochemistry, Vol. 126, 109571, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats
AU - Wu, Kay Li Hui
AU - Liu, Wen Chung
AU - Wu, Chih Wei
AU - Fu, Mu Hui
AU - Huang, Hsiu Mei
AU - Tain, You Lin
AU - Liang, Chih Kuang
AU - Hung, Chun Ying
AU - Chen, I. Chun
AU - Hung, Pi Lien
AU - Lin, Yu Ju
AU - Hirase, Hajime
N1 - Publisher Copyright: © 2024 Elsevier Inc.
PY - 2024
Y1 - 2024
N2 - Maternal nutrient intake influences the health of the offspring via microenvironmental systems in digestion and absorption. Maternal high fructose diet (HFD) impairs hippocampus-dependent memory in adult female rat offspring. However, the underlying mechanisms remain largely unclear. Maternal HFD causes microbiota dysbiosis. In this study, we find that the plasma level of butyrate, a major metabolite of microbiota, is significantly decreased in the adult female maternal HFD offspring. In these rats, GPR43, a butyrate receptor was downregulated in the hippocampus. Moreover, the expressions of mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) were downregulated in the hippocampus. The decreases of these functional proteins were reversed by fructooligosaccharides (FOS, a probiotic) treatment in adulthood. Astrocytes are critical for energy metabolism in the brain. Primary astrocyte culture from female maternal HFD offspring indicated that GPR43 and the mitochondrial biogenesis were significantly suppressed, which was reversed by supplemental butyrate incubation. The oxygen consumption rate (OCR) was reduced in the HFD group and rescued by butyrate. Intriguingly, the nuclear histone deacetylase 4 (HDAC4) was enhanced in the HFD group, suggesting an inhibitory role of butyrate on histone deacetylase activity. Inhibition of HDAC4 effectively restored the OCR, bioenergetics, and biogenesis of mitochondria. Together, these results suggested that the impaired butyrate signaling by maternal HFD could underlie the reduced mitochondrial functions in the hippocampus via HDAC4-mediated epigenetic changes.
AB - Maternal nutrient intake influences the health of the offspring via microenvironmental systems in digestion and absorption. Maternal high fructose diet (HFD) impairs hippocampus-dependent memory in adult female rat offspring. However, the underlying mechanisms remain largely unclear. Maternal HFD causes microbiota dysbiosis. In this study, we find that the plasma level of butyrate, a major metabolite of microbiota, is significantly decreased in the adult female maternal HFD offspring. In these rats, GPR43, a butyrate receptor was downregulated in the hippocampus. Moreover, the expressions of mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) were downregulated in the hippocampus. The decreases of these functional proteins were reversed by fructooligosaccharides (FOS, a probiotic) treatment in adulthood. Astrocytes are critical for energy metabolism in the brain. Primary astrocyte culture from female maternal HFD offspring indicated that GPR43 and the mitochondrial biogenesis were significantly suppressed, which was reversed by supplemental butyrate incubation. The oxygen consumption rate (OCR) was reduced in the HFD group and rescued by butyrate. Intriguingly, the nuclear histone deacetylase 4 (HDAC4) was enhanced in the HFD group, suggesting an inhibitory role of butyrate on histone deacetylase activity. Inhibition of HDAC4 effectively restored the OCR, bioenergetics, and biogenesis of mitochondria. Together, these results suggested that the impaired butyrate signaling by maternal HFD could underlie the reduced mitochondrial functions in the hippocampus via HDAC4-mediated epigenetic changes.
KW - Bioenergetics
KW - Butyrate
KW - GPR43
KW - HDAC4
KW - Maternal high fructose diet
KW - Mitochondrial biogenesis
U2 - 10.1016/j.jnutbio.2024.109571
DO - 10.1016/j.jnutbio.2024.109571
M3 - Journal article
C2 - 38199310
AN - SCOPUS:85183042718
VL - 126
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
SN - 0955-2863
M1 - 109571
ER -
ID: 381235805