TY - JOUR
T1 - Ingestion of eicosapentaenoic acid in the early stage of social isolation reduces a fibroblast growth factor 21 resistant state independently of body weight in KKAy mice
AU - Nonogaki, Katsunori
AU - Yamazaki, Tomoe
AU - Murakami, Mari
AU - Kaji, Takao
PY - 2015/7/30
Y1 - 2015/7/30
N2 - Fibroblast growth factor (FGF) 21 is a mediator of glucose and lipid metabolism. Although exogenous administration of FGF21 exerts beneficial effects on glucose and lipid metabolism, circulating FGF21 levels are elevated in ob/ob and db/db mice, diet-induced obese mice and obese human. Here we show that ingestion of eicosapentaenoic acid (EPA) for 6 days after individually-housing significantly suppressed the hyperglycemia and hypertriglyceridemia associated with decreases in plasma insulin and FGF21 levels in KKAy mice while having no effects on food intake, body weight or plasma active GLP-1 levels. The ingestion of EPA had no significant effects on the expression of FGF21 in the liver, epididymal white adipose tissue and skeletal muscle. Moreover, the ingestion of EPA significantly decreased the expression of hepatic peroxisome sterol regulatory element-binding protein (SREBP1c), carbohydrate response element-binding protein (ChREBP), stearoyl-CoA deaturase and periostin, which are involved in hepatic lipogenesis and hepatosteaotosis, in KKAy mice. On the other hand, the ingestion of EPA had no significant effects on expression of hepatic gp78, Notch, forkhead box protein O1 or glucose-6-phosphatase. These findings suggest that EPA ingestion in the early stage of social isolation suppresses hyperglycemia and hypertriglyceridemia associated with reduced FGF21 and insulin resistance without altering food intake and body weight, and that the EPA ingestion suppresses hepatic lipogenesis by suppressing Notch- and gp78-independent SEREBP1c and ChREBP pathways in KKAy mice.
AB - Fibroblast growth factor (FGF) 21 is a mediator of glucose and lipid metabolism. Although exogenous administration of FGF21 exerts beneficial effects on glucose and lipid metabolism, circulating FGF21 levels are elevated in ob/ob and db/db mice, diet-induced obese mice and obese human. Here we show that ingestion of eicosapentaenoic acid (EPA) for 6 days after individually-housing significantly suppressed the hyperglycemia and hypertriglyceridemia associated with decreases in plasma insulin and FGF21 levels in KKAy mice while having no effects on food intake, body weight or plasma active GLP-1 levels. The ingestion of EPA had no significant effects on the expression of FGF21 in the liver, epididymal white adipose tissue and skeletal muscle. Moreover, the ingestion of EPA significantly decreased the expression of hepatic peroxisome sterol regulatory element-binding protein (SREBP1c), carbohydrate response element-binding protein (ChREBP), stearoyl-CoA deaturase and periostin, which are involved in hepatic lipogenesis and hepatosteaotosis, in KKAy mice. On the other hand, the ingestion of EPA had no significant effects on expression of hepatic gp78, Notch, forkhead box protein O1 or glucose-6-phosphatase. These findings suggest that EPA ingestion in the early stage of social isolation suppresses hyperglycemia and hypertriglyceridemia associated with reduced FGF21 and insulin resistance without altering food intake and body weight, and that the EPA ingestion suppresses hepatic lipogenesis by suppressing Notch- and gp78-independent SEREBP1c and ChREBP pathways in KKAy mice.
KW - ChREBP
KW - EPA
KW - FGF21
KW - GLP-1
KW - Hyperglycemia
KW - Hypertriglyceridemia
KW - Lipogenesis
KW - Notch
KW - Periostin
KW - SREBP1c
KW - gp78
UR - http://www.scopus.com/inward/record.url?scp=84938421310&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938421310&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2015.07.058
DO - 10.1016/j.bbrc.2015.07.058
M3 - Article
C2 - 26187667
AN - SCOPUS:84938421310
VL - 464
SP - 674
EP - 677
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -