Abstract
Insulin is a key molecule that synchronizes peripheral clocks, such as that in the liver. Although we previously reported that mice fed a low-protein diet showed altered expression of lipid-related genes in the liver and induction of hepatic steatosis, it is unknown whether a low-protein diet impairs insulin secretion and modifies the hepatic circadian rhythm. Therefore, we investigated the effects of the intake of a low-protein diet on the circadian rhythm of insulin secretion and hepatic lipid metabolism in mice. Under 12-h light/12-h dark cycle, mice fed a low-protein diet for 7 days displayed enhanced food intake at the end of the light phase, although central and peripheral PER2 expression rhythm was maintained. Serum insulin levels in mice fed a low-protein diet remained low during the day, and the insulin secretion in OGTT was also markedly lower than in normal mice. In mice fed low-protein diet, hepatic TG accumulation was observed during the nighttime, with relatively high levels of ACC1 mRNA and total ACC proteins. Although there were no differences in the activity rhythm of hepatic mTOR between mice fed a normal or low-protein diet, hepatic IRS-2 expression in mice fed a low-protein diet remained low during the day, with no increase at the beginning of the light period. These results suggested that the low-protein diet eliminated the circadian rhythm of serum insulin and hepatic lipid metabolism in mice, providing insights into our understanding of the mechanisms of hepatic disorders of lipid metabolism.
| Original language | English |
|---|---|
| Pages (from-to) | 177-185 |
| Number of pages | 9 |
| Journal | Journal of Nutritional Biochemistry |
| Volume | 63 |
| DOIs | |
| Publication status | Published - 2019 Jan 1 |
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Keywords
- Fatty liver
- Insulin receptor substrate
- Lipogenesis
- Mammalian target of rapamycin
- Metabolic syndrome
- Steatosis
- Triglyceride
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Molecular Biology
- Nutrition and Dietetics
- Clinical Biochemistry
Cite this
A low-protein diet eliminates the circadian rhythm of serum insulin and hepatic lipid metabolism in mice. / Yokota, Shin Ichi; Nakamura, Kaai; Ando, Midori; Haraguchi, Atsushi; Omori, Kanako; Shibata, Shigenobu.
In: Journal of Nutritional Biochemistry, Vol. 63, 01.01.2019, p. 177-185.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A low-protein diet eliminates the circadian rhythm of serum insulin and hepatic lipid metabolism in mice
AU - Yokota, Shin Ichi
AU - Nakamura, Kaai
AU - Ando, Midori
AU - Haraguchi, Atsushi
AU - Omori, Kanako
AU - Shibata, Shigenobu
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Insulin is a key molecule that synchronizes peripheral clocks, such as that in the liver. Although we previously reported that mice fed a low-protein diet showed altered expression of lipid-related genes in the liver and induction of hepatic steatosis, it is unknown whether a low-protein diet impairs insulin secretion and modifies the hepatic circadian rhythm. Therefore, we investigated the effects of the intake of a low-protein diet on the circadian rhythm of insulin secretion and hepatic lipid metabolism in mice. Under 12-h light/12-h dark cycle, mice fed a low-protein diet for 7 days displayed enhanced food intake at the end of the light phase, although central and peripheral PER2 expression rhythm was maintained. Serum insulin levels in mice fed a low-protein diet remained low during the day, and the insulin secretion in OGTT was also markedly lower than in normal mice. In mice fed low-protein diet, hepatic TG accumulation was observed during the nighttime, with relatively high levels of ACC1 mRNA and total ACC proteins. Although there were no differences in the activity rhythm of hepatic mTOR between mice fed a normal or low-protein diet, hepatic IRS-2 expression in mice fed a low-protein diet remained low during the day, with no increase at the beginning of the light period. These results suggested that the low-protein diet eliminated the circadian rhythm of serum insulin and hepatic lipid metabolism in mice, providing insights into our understanding of the mechanisms of hepatic disorders of lipid metabolism.
AB - Insulin is a key molecule that synchronizes peripheral clocks, such as that in the liver. Although we previously reported that mice fed a low-protein diet showed altered expression of lipid-related genes in the liver and induction of hepatic steatosis, it is unknown whether a low-protein diet impairs insulin secretion and modifies the hepatic circadian rhythm. Therefore, we investigated the effects of the intake of a low-protein diet on the circadian rhythm of insulin secretion and hepatic lipid metabolism in mice. Under 12-h light/12-h dark cycle, mice fed a low-protein diet for 7 days displayed enhanced food intake at the end of the light phase, although central and peripheral PER2 expression rhythm was maintained. Serum insulin levels in mice fed a low-protein diet remained low during the day, and the insulin secretion in OGTT was also markedly lower than in normal mice. In mice fed low-protein diet, hepatic TG accumulation was observed during the nighttime, with relatively high levels of ACC1 mRNA and total ACC proteins. Although there were no differences in the activity rhythm of hepatic mTOR between mice fed a normal or low-protein diet, hepatic IRS-2 expression in mice fed a low-protein diet remained low during the day, with no increase at the beginning of the light period. These results suggested that the low-protein diet eliminated the circadian rhythm of serum insulin and hepatic lipid metabolism in mice, providing insights into our understanding of the mechanisms of hepatic disorders of lipid metabolism.
KW - Fatty liver
KW - Insulin receptor substrate
KW - Lipogenesis
KW - Mammalian target of rapamycin
KW - Metabolic syndrome
KW - Steatosis
KW - Triglyceride
UR - http://www.scopus.com/inward/record.url?scp=85056157648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056157648&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2018.10.004
DO - 10.1016/j.jnutbio.2018.10.004
M3 - Article
VL - 63
SP - 177
EP - 185
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
SN - 0955-2863
ER -