Limits...
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.

Show MeSH

Related in: MedlinePlus

C3 and C5a plasma level and mRNA expression in muscle and liver of genes implicated in substrate utilization.Plasma levels of C3 (A) and C5a (B) in WT and C5aRKO on chow and DIO diet for n = 8–12 per group. Gene expression in quadriceps muscle tissue (C) and liver (D) for fatty acid transporter (CD36), fatty acid synthase (FAS), lipoprotein lipase (LPL), diacylglycerolacyltransferase-1 (DGAT1), diacylglycerolacyltransferase-2 (DGAT2) and peroxisome-proliferator activated receptor gamma (PPARG) were measured in WT CHOW diet (open bars), C5aRKO CHOW (solid bars), WT diet-induced obesity (DIO) diet (checkered bars) and C5aRKO DIO (striped bars) for n = 6–12 per group. Results are expressed as means ± SEM; statistical differences were determined by t-test, where *P<0.05 and**P<0.001 and ***P<0.0001 for C5aRKO vs WT on the same diet, unless otherwise indicated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646841&req=5

pone-0062531-g005: C3 and C5a plasma level and mRNA expression in muscle and liver of genes implicated in substrate utilization.Plasma levels of C3 (A) and C5a (B) in WT and C5aRKO on chow and DIO diet for n = 8–12 per group. Gene expression in quadriceps muscle tissue (C) and liver (D) for fatty acid transporter (CD36), fatty acid synthase (FAS), lipoprotein lipase (LPL), diacylglycerolacyltransferase-1 (DGAT1), diacylglycerolacyltransferase-2 (DGAT2) and peroxisome-proliferator activated receptor gamma (PPARG) were measured in WT CHOW diet (open bars), C5aRKO CHOW (solid bars), WT diet-induced obesity (DIO) diet (checkered bars) and C5aRKO DIO (striped bars) for n = 6–12 per group. Results are expressed as means ± SEM; statistical differences were determined by t-test, where *P<0.05 and**P<0.001 and ***P<0.0001 for C5aRKO vs WT on the same diet, unless otherwise indicated.

Mentions: While there was no change in circulating ASP (data not shown), C3 plasma levels were lower in C5aRKO mice when compared to their WT counterparts (Fig 5A), while C5a plasma level was influenced by the DIO diet only in the WT group (Fig. 5 B).


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)

C3 and C5a plasma level and mRNA expression in muscle and liver of genes implicated in substrate utilization.Plasma levels of C3 (A) and C5a (B) in WT and C5aRKO on chow and DIO diet for n = 8–12 per group. Gene expression in quadriceps muscle tissue (C) and liver (D) for fatty acid transporter (CD36), fatty acid synthase (FAS), lipoprotein lipase (LPL), diacylglycerolacyltransferase-1 (DGAT1), diacylglycerolacyltransferase-2 (DGAT2) and peroxisome-proliferator activated receptor gamma (PPARG) were measured in WT CHOW diet (open bars), C5aRKO CHOW (solid bars), WT diet-induced obesity (DIO) diet (checkered bars) and C5aRKO DIO (striped bars) for n = 6–12 per group. Results are expressed as means ± SEM; statistical differences were determined by t-test, where *P<0.05 and**P<0.001 and ***P<0.0001 for C5aRKO vs WT on the same diet, unless otherwise indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646841&req=5

pone-0062531-g005: C3 and C5a plasma level and mRNA expression in muscle and liver of genes implicated in substrate utilization.Plasma levels of C3 (A) and C5a (B) in WT and C5aRKO on chow and DIO diet for n = 8–12 per group. Gene expression in quadriceps muscle tissue (C) and liver (D) for fatty acid transporter (CD36), fatty acid synthase (FAS), lipoprotein lipase (LPL), diacylglycerolacyltransferase-1 (DGAT1), diacylglycerolacyltransferase-2 (DGAT2) and peroxisome-proliferator activated receptor gamma (PPARG) were measured in WT CHOW diet (open bars), C5aRKO CHOW (solid bars), WT diet-induced obesity (DIO) diet (checkered bars) and C5aRKO DIO (striped bars) for n = 6–12 per group. Results are expressed as means ± SEM; statistical differences were determined by t-test, where *P<0.05 and**P<0.001 and ***P<0.0001 for C5aRKO vs WT on the same diet, unless otherwise indicated.
Mentions: While there was no change in circulating ASP (data not shown), C3 plasma levels were lower in C5aRKO mice when compared to their WT counterparts (Fig 5A), while C5a plasma level was influenced by the DIO diet only in the WT group (Fig. 5 B).

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