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C5a receptor deficiency alters energy utilization and fat storage.

Roy C, Gupta A, Fisette A, Lapointe M, Poursharifi P, Richard D, Lu H, Lu B, Gerard N, Gerard C, Cianflone K - PLoS ONE (2013)

Bottom Line: Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload.Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW) and liver (CHOW and DIO) and PPARγ was increased in muscle and liver.These observations point towards a role (either direct or indirect) for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Québec, Canada.

ABSTRACT

Objective: To investigate the impact of whole body C5a receptor (C5aR) deficiency on energy metabolism and fat storage.

Design: Male wildtype (WT) and C5aR knockout (C5aRKO) mice were fed a low fat (CHOW) or a high fat high sucrose diet-induced obesity (DIO) diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR.

Results: At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (-7% CHOW, -12% DIO) as well as smaller gonadal (-38% CHOW, -36% DIO) and inguinal (-29% CHOW, -30% DIO) fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW) and liver (CHOW and DIO) and PPARγ was increased in muscle and liver.

Conclusion: These observations point towards a role (either direct or indirect) for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

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Related in: MedlinePlus

Metabolic response to glucose and insulin tolerance tests and postprandial lipid clearance in C5aRKO mice.(A): Plasma glucose levels following an intraperitoneal injection of glucose in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of low fat CHOW or diet-induced obesity (DIO) diet for n = 6–7 mice per group. (B): Plasma glucose levels following an intra-peritoneal injection of insulin in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of CHOW or DIO diet for n = 6–7 mice per group. Triglyceride (TG; C and D) postprandial lipid clearance following an oral fat load for WT (open symbols), C5aRKO (solid symbols) mice on CHOW (C) and diet-induced obesity (DIO) (D) diets for n = 5 mice per group. Results are presented as means ± SEM; data are analysed by 2-way RM-ANOVA followed by Bonferroni post-test for individual time point differences, where *P<0.05, and **P<0.001 for KO vs. WT and by t-test for the incremental area-under-the curve (IAUC), where *P<0.05 vs WT on the same diet.
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pone-0062531-g004: Metabolic response to glucose and insulin tolerance tests and postprandial lipid clearance in C5aRKO mice.(A): Plasma glucose levels following an intraperitoneal injection of glucose in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of low fat CHOW or diet-induced obesity (DIO) diet for n = 6–7 mice per group. (B): Plasma glucose levels following an intra-peritoneal injection of insulin in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of CHOW or DIO diet for n = 6–7 mice per group. Triglyceride (TG; C and D) postprandial lipid clearance following an oral fat load for WT (open symbols), C5aRKO (solid symbols) mice on CHOW (C) and diet-induced obesity (DIO) (D) diets for n = 5 mice per group. Results are presented as means ± SEM; data are analysed by 2-way RM-ANOVA followed by Bonferroni post-test for individual time point differences, where *P<0.05, and **P<0.001 for KO vs. WT and by t-test for the incremental area-under-the curve (IAUC), where *P<0.05 vs WT on the same diet.

Mentions: Insulin-related metabolism was further evaluated in detail under fasting conditions, as well as following insulin sensitivity tests. Fasting blood glucose levels were similar in all 4 groups and while fasting blood insulin levels were identical between C5aRKO and the WT mice on the same diet, the WT mice on the DIO diet had increased insulin levels as compared to their CHOW counterparts (Table 1). At week 13, both glucose and insulin tolerance tests were administered to assess insulin sensitivity on both CHOW and DIO diets (Fig. 4 A and B). In spite of the decreased body and adipose tissue weights, blood glucose excursion in both groups of C5aRKO mice was not different during the glucose tolerance test (GTT) (Fig. 4A). Additionally, no significant difference in the insulin-induced decrease in blood glucose during the insulin tolerance test (ITT) was detected in the C5aRKO mice on either diet compared with WT mice (Fig. 4B). Furthermore, there was no difference in IRS1 expression in adipose, skeletal muscle and liver tissues (data not shown).


C5a receptor deficiency alters energy utilization and fat storage.

Roy C, Gupta A, Fisette A, Lapointe M, Poursharifi P, Richard D, Lu H, Lu B, Gerard N, Gerard C, Cianflone K - PLoS ONE (2013)

Metabolic response to glucose and insulin tolerance tests and postprandial lipid clearance in C5aRKO mice.(A): Plasma glucose levels following an intraperitoneal injection of glucose in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of low fat CHOW or diet-induced obesity (DIO) diet for n = 6–7 mice per group. (B): Plasma glucose levels following an intra-peritoneal injection of insulin in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of CHOW or DIO diet for n = 6–7 mice per group. Triglyceride (TG; C and D) postprandial lipid clearance following an oral fat load for WT (open symbols), C5aRKO (solid symbols) mice on CHOW (C) and diet-induced obesity (DIO) (D) diets for n = 5 mice per group. Results are presented as means ± SEM; data are analysed by 2-way RM-ANOVA followed by Bonferroni post-test for individual time point differences, where *P<0.05, and **P<0.001 for KO vs. WT and by t-test for the incremental area-under-the curve (IAUC), where *P<0.05 vs WT on the same diet.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3646841&req=5

pone-0062531-g004: Metabolic response to glucose and insulin tolerance tests and postprandial lipid clearance in C5aRKO mice.(A): Plasma glucose levels following an intraperitoneal injection of glucose in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of low fat CHOW or diet-induced obesity (DIO) diet for n = 6–7 mice per group. (B): Plasma glucose levels following an intra-peritoneal injection of insulin in WT (open symbols) and C5aRKO (solid symbols) mice after 13 weeks of CHOW or DIO diet for n = 6–7 mice per group. Triglyceride (TG; C and D) postprandial lipid clearance following an oral fat load for WT (open symbols), C5aRKO (solid symbols) mice on CHOW (C) and diet-induced obesity (DIO) (D) diets for n = 5 mice per group. Results are presented as means ± SEM; data are analysed by 2-way RM-ANOVA followed by Bonferroni post-test for individual time point differences, where *P<0.05, and **P<0.001 for KO vs. WT and by t-test for the incremental area-under-the curve (IAUC), where *P<0.05 vs WT on the same diet.
Mentions: Insulin-related metabolism was further evaluated in detail under fasting conditions, as well as following insulin sensitivity tests. Fasting blood glucose levels were similar in all 4 groups and while fasting blood insulin levels were identical between C5aRKO and the WT mice on the same diet, the WT mice on the DIO diet had increased insulin levels as compared to their CHOW counterparts (Table 1). At week 13, both glucose and insulin tolerance tests were administered to assess insulin sensitivity on both CHOW and DIO diets (Fig. 4 A and B). In spite of the decreased body and adipose tissue weights, blood glucose excursion in both groups of C5aRKO mice was not different during the glucose tolerance test (GTT) (Fig. 4A). Additionally, no significant difference in the insulin-induced decrease in blood glucose during the insulin tolerance test (ITT) was detected in the C5aRKO mice on either diet compared with WT mice (Fig. 4B). Furthermore, there was no difference in IRS1 expression in adipose, skeletal muscle and liver tissues (data not shown).

Bottom Line: Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload.Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW) and liver (CHOW and DIO) and PPARγ was increased in muscle and liver.These observations point towards a role (either direct or indirect) for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Québec, Canada.

ABSTRACT

Objective: To investigate the impact of whole body C5a receptor (C5aR) deficiency on energy metabolism and fat storage.

Design: Male wildtype (WT) and C5aR knockout (C5aRKO) mice were fed a low fat (CHOW) or a high fat high sucrose diet-induced obesity (DIO) diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR.

Results: At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (-7% CHOW, -12% DIO) as well as smaller gonadal (-38% CHOW, -36% DIO) and inguinal (-29% CHOW, -30% DIO) fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW) and liver (CHOW and DIO) and PPARγ was increased in muscle and liver.

Conclusion: These observations point towards a role (either direct or indirect) for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

Show MeSH
Related in: MedlinePlus