Limits...
Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in Insr(P1195L/+) mice fed high-fat-diet.

Lee EY, Sakurai K, Zhang X, Toda C, Tanaka T, Jiang M, Shirasawa T, Tachibana K, Yokote K, Vidal-Puig A, Minokoshi Y, Miki T - Sci Rep (2015)

Bottom Line: We found that the expressions of genes involved in bile acid (BA) metabolism were altered in Insr(P1195L/+)/HFD liver.Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in Insr(P1195L/+)/HFD liver.These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in Insr(P1195L/+)/HFD liver.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670 Japan.

ABSTRACT
High-fat diet (HFD) triggers insulin resistance and diabetes mellitus, but their link remains unclear. Characterization of overt hyperglycemia in insulin receptor mutant (Insr(P1195L/+)) mice exposed to HFD (Insr(P1195L/+)/HFD mice) revealed increased glucose-6-phosphatase (G6pc) expression in liver and increased gluconeogenesis from glycerol. Lipolysis in white adipose tissues (WAT) and lipolysis-induced blood glucose rise were increased in Insr(P1195L/+)/HFD mice, while wild-type WAT transplantation ameliorated the hyperglycemia and the increased G6pc expression. We found that the expressions of genes involved in bile acid (BA) metabolism were altered in Insr(P1195L/+)/HFD liver. Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in Insr(P1195L/+)/HFD liver. Reduced Cyp7a1 expression in Insr(P1195L/+)/HFD liver was rescued by WAT transplantation, and the expression of Cyp7a1 was suppressed by glycerol administration in wild-type liver. These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in Insr(P1195L/+)/HFD liver.

No MeSH data available.


Related in: MedlinePlus

Supplementation with either CA or UDCA ameliorated hyperglycemia of InsrP1195L/+/HFD mice.(a,b) Changes in body weight (a) and blood glucose levels (b). (c) mRNA expressions of G6pc in liver in fasted and refed conditions (n = 5–8 per each group). *,†only the statistical difference between supplementation with or without CA in InsrP1195L/+/HFD mice (*) and in WT/HFD (†) is depicted by symbols in (a,b). Data are mean ± SEM. Significance between treatment at individual time points by two-tailed Student’s t-test (a,b). Two-way ANOVA plus Bonferroni post-hoc analysis (c). *,†P < 0.05, **,††P < 0.01, ***,†††P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4663474&req=5

f7: Supplementation with either CA or UDCA ameliorated hyperglycemia of InsrP1195L/+/HFD mice.(a,b) Changes in body weight (a) and blood glucose levels (b). (c) mRNA expressions of G6pc in liver in fasted and refed conditions (n = 5–8 per each group). *,†only the statistical difference between supplementation with or without CA in InsrP1195L/+/HFD mice (*) and in WT/HFD (†) is depicted by symbols in (a,b). Data are mean ± SEM. Significance between treatment at individual time points by two-tailed Student’s t-test (a,b). Two-way ANOVA plus Bonferroni post-hoc analysis (c). *,†P < 0.05, **,††P < 0.01, ***,†††P < 0.001.

Mentions: Recent studies have shown that BAs play an important role in the regulation of energy and glucose metabolism. Various molecules including the farnesoid X receptor (FXR)14 and the G-protein coupled receptor TGR515 are known to be involved in the BA-medicated metabolic regulation. In accord with the previous reports16, we found that supplementation with CA significantly decreased the gain in body weight in both WT/HFD and InsrP1195L/+/HFD mice (Fig. 7a). In addition, supplementation with ursodeoxycholic acid (UDCA) elicited a reduced body weight gain similar to that by CA supplementation. Notably, the supplementation with either CA or UDCA restored euglycemia in InsrP1195L/+/HFD mice (Fig. 7b) and prevented the rise in G6pc expression on re-feeding (Fig. 7c), suggesting that alteration in BAs may influence glucose homeostasis in InsrP1195L/+/HFD mice.


Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in Insr(P1195L/+) mice fed high-fat-diet.

Lee EY, Sakurai K, Zhang X, Toda C, Tanaka T, Jiang M, Shirasawa T, Tachibana K, Yokote K, Vidal-Puig A, Minokoshi Y, Miki T - Sci Rep (2015)

Supplementation with either CA or UDCA ameliorated hyperglycemia of InsrP1195L/+/HFD mice.(a,b) Changes in body weight (a) and blood glucose levels (b). (c) mRNA expressions of G6pc in liver in fasted and refed conditions (n = 5–8 per each group). *,†only the statistical difference between supplementation with or without CA in InsrP1195L/+/HFD mice (*) and in WT/HFD (†) is depicted by symbols in (a,b). Data are mean ± SEM. Significance between treatment at individual time points by two-tailed Student’s t-test (a,b). Two-way ANOVA plus Bonferroni post-hoc analysis (c). *,†P < 0.05, **,††P < 0.01, ***,†††P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663474&req=5

f7: Supplementation with either CA or UDCA ameliorated hyperglycemia of InsrP1195L/+/HFD mice.(a,b) Changes in body weight (a) and blood glucose levels (b). (c) mRNA expressions of G6pc in liver in fasted and refed conditions (n = 5–8 per each group). *,†only the statistical difference between supplementation with or without CA in InsrP1195L/+/HFD mice (*) and in WT/HFD (†) is depicted by symbols in (a,b). Data are mean ± SEM. Significance between treatment at individual time points by two-tailed Student’s t-test (a,b). Two-way ANOVA plus Bonferroni post-hoc analysis (c). *,†P < 0.05, **,††P < 0.01, ***,†††P < 0.001.
Mentions: Recent studies have shown that BAs play an important role in the regulation of energy and glucose metabolism. Various molecules including the farnesoid X receptor (FXR)14 and the G-protein coupled receptor TGR515 are known to be involved in the BA-medicated metabolic regulation. In accord with the previous reports16, we found that supplementation with CA significantly decreased the gain in body weight in both WT/HFD and InsrP1195L/+/HFD mice (Fig. 7a). In addition, supplementation with ursodeoxycholic acid (UDCA) elicited a reduced body weight gain similar to that by CA supplementation. Notably, the supplementation with either CA or UDCA restored euglycemia in InsrP1195L/+/HFD mice (Fig. 7b) and prevented the rise in G6pc expression on re-feeding (Fig. 7c), suggesting that alteration in BAs may influence glucose homeostasis in InsrP1195L/+/HFD mice.

Bottom Line: We found that the expressions of genes involved in bile acid (BA) metabolism were altered in Insr(P1195L/+)/HFD liver.Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in Insr(P1195L/+)/HFD liver.These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in Insr(P1195L/+)/HFD liver.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670 Japan.

ABSTRACT
High-fat diet (HFD) triggers insulin resistance and diabetes mellitus, but their link remains unclear. Characterization of overt hyperglycemia in insulin receptor mutant (Insr(P1195L/+)) mice exposed to HFD (Insr(P1195L/+)/HFD mice) revealed increased glucose-6-phosphatase (G6pc) expression in liver and increased gluconeogenesis from glycerol. Lipolysis in white adipose tissues (WAT) and lipolysis-induced blood glucose rise were increased in Insr(P1195L/+)/HFD mice, while wild-type WAT transplantation ameliorated the hyperglycemia and the increased G6pc expression. We found that the expressions of genes involved in bile acid (BA) metabolism were altered in Insr(P1195L/+)/HFD liver. Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in Insr(P1195L/+)/HFD liver. Reduced Cyp7a1 expression in Insr(P1195L/+)/HFD liver was rescued by WAT transplantation, and the expression of Cyp7a1 was suppressed by glycerol administration in wild-type liver. These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in Insr(P1195L/+)/HFD liver.

No MeSH data available.


Related in: MedlinePlus