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

InsrP1195L/+/HFD mice exhibit glucose intolerance, insulin resistance, and increased gluconeogenesis from glycerol.(a) Blood glucose levels of InsrP1195L/+ and WT mice fed ad libitum (n = 8–10 per each group). (b) Body weight of InsrP1195L/+ and WT mice (n = 8–10 per each group). (c) OGTT (n = 8–10 per each group). (d) ITT (n = 6–10 per each group). (e,f) mRNA expressions of Pck1 (e) and G6pc (f) in liver (n = 10–12 per each group). (g,h) Blood glucose levels after pyruvate (g) and glycerol (h) administration (n = 10–12 per each group). Data are mean ± SEM. Only the statistical difference between WT/HFD and InsrP1195L/+/HFD mice is depicted by asterisks in (a–d,g,h). Significance between strains (WT/HFD and InsrP1195L/+/HFD mice) at individual time points by two-tailed Student’s t-test (a–d,g,h). Two-way ANOVA plus Bonferroni post-hoc analysis (e,f). *P < 0.05, **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: InsrP1195L/+/HFD mice exhibit glucose intolerance, insulin resistance, and increased gluconeogenesis from glycerol.(a) Blood glucose levels of InsrP1195L/+ and WT mice fed ad libitum (n = 8–10 per each group). (b) Body weight of InsrP1195L/+ and WT mice (n = 8–10 per each group). (c) OGTT (n = 8–10 per each group). (d) ITT (n = 6–10 per each group). (e,f) mRNA expressions of Pck1 (e) and G6pc (f) in liver (n = 10–12 per each group). (g,h) Blood glucose levels after pyruvate (g) and glycerol (h) administration (n = 10–12 per each group). Data are mean ± SEM. Only the statistical difference between WT/HFD and InsrP1195L/+/HFD mice is depicted by asterisks in (a–d,g,h). Significance between strains (WT/HFD and InsrP1195L/+/HFD mice) at individual time points by two-tailed Student’s t-test (a–d,g,h). Two-way ANOVA plus Bonferroni post-hoc analysis (e,f). *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: The blood glucose levels of InsrP1195L/+ mice under normal diet (ND) (InsrP1195L/+/ND mice) were not different from those of wild-type (WT) mice; however, InsrP1195L/+ mice under HFD (InsrP1195L/+/HFD mice) developed hyperglycemia (Fig. 1a). The expected increase in body weight of InsrP1195L/+/HFD mice was significantly blunted (Fig. 1b). Glucose intolerance in InsrP1195L/+/HFD mice was confirmed by oral glucose tolerance test (OGTT) (Fig. 1c). In addition, the glucose lowering effect of insulin was severely impaired in InsrP1195L/+/HFD mice, as assessed by insulin tolerance test (ITT) (Fig. 1d).


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)

InsrP1195L/+/HFD mice exhibit glucose intolerance, insulin resistance, and increased gluconeogenesis from glycerol.(a) Blood glucose levels of InsrP1195L/+ and WT mice fed ad libitum (n = 8–10 per each group). (b) Body weight of InsrP1195L/+ and WT mice (n = 8–10 per each group). (c) OGTT (n = 8–10 per each group). (d) ITT (n = 6–10 per each group). (e,f) mRNA expressions of Pck1 (e) and G6pc (f) in liver (n = 10–12 per each group). (g,h) Blood glucose levels after pyruvate (g) and glycerol (h) administration (n = 10–12 per each group). Data are mean ± SEM. Only the statistical difference between WT/HFD and InsrP1195L/+/HFD mice is depicted by asterisks in (a–d,g,h). Significance between strains (WT/HFD and InsrP1195L/+/HFD mice) at individual time points by two-tailed Student’s t-test (a–d,g,h). Two-way ANOVA plus Bonferroni post-hoc analysis (e,f). *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

f1: InsrP1195L/+/HFD mice exhibit glucose intolerance, insulin resistance, and increased gluconeogenesis from glycerol.(a) Blood glucose levels of InsrP1195L/+ and WT mice fed ad libitum (n = 8–10 per each group). (b) Body weight of InsrP1195L/+ and WT mice (n = 8–10 per each group). (c) OGTT (n = 8–10 per each group). (d) ITT (n = 6–10 per each group). (e,f) mRNA expressions of Pck1 (e) and G6pc (f) in liver (n = 10–12 per each group). (g,h) Blood glucose levels after pyruvate (g) and glycerol (h) administration (n = 10–12 per each group). Data are mean ± SEM. Only the statistical difference between WT/HFD and InsrP1195L/+/HFD mice is depicted by asterisks in (a–d,g,h). Significance between strains (WT/HFD and InsrP1195L/+/HFD mice) at individual time points by two-tailed Student’s t-test (a–d,g,h). Two-way ANOVA plus Bonferroni post-hoc analysis (e,f). *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: The blood glucose levels of InsrP1195L/+ mice under normal diet (ND) (InsrP1195L/+/ND mice) were not different from those of wild-type (WT) mice; however, InsrP1195L/+ mice under HFD (InsrP1195L/+/HFD mice) developed hyperglycemia (Fig. 1a). The expected increase in body weight of InsrP1195L/+/HFD mice was significantly blunted (Fig. 1b). Glucose intolerance in InsrP1195L/+/HFD mice was confirmed by oral glucose tolerance test (OGTT) (Fig. 1c). In addition, the glucose lowering effect of insulin was severely impaired in InsrP1195L/+/HFD mice, as assessed by insulin tolerance test (ITT) (Fig. 1d).

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