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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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C5aR and C5L2 expression in adipose, muscle and liver of mice.C5aR mRNA expression for WT CHOW (open bars) and WT diet-induced obesity (DIO) (checkered bars) for (A) gonadal adipose tissue, (B) quadriceps muscle, and (C) liver were measured. C5L2 mRNA expression for WT CHOW (open bars), WT DIO (checkered bars), KO CHOW (black bars) and KO DIO (striped bars) for (D) gonadal adipose tissue, (E) quadriceps muscle, and (F) liver were evaluated. Results are expressed as means ± SEM; n = 9–12 per group. Statistical differences were determined by t-test, for C5aRKO vs WT on their respective diets where *P<0.05, **P<0.001 and ***P<0.0001.
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pone-0062531-g003: C5aR and C5L2 expression in adipose, muscle and liver of mice.C5aR mRNA expression for WT CHOW (open bars) and WT diet-induced obesity (DIO) (checkered bars) for (A) gonadal adipose tissue, (B) quadriceps muscle, and (C) liver were measured. C5L2 mRNA expression for WT CHOW (open bars), WT DIO (checkered bars), KO CHOW (black bars) and KO DIO (striped bars) for (D) gonadal adipose tissue, (E) quadriceps muscle, and (F) liver were evaluated. Results are expressed as means ± SEM; n = 9–12 per group. Statistical differences were determined by t-test, for C5aRKO vs WT on their respective diets where *P<0.05, **P<0.001 and ***P<0.0001.

Mentions: Although C5a-C5aR functions have been largely investigated from the perspective of an immune response, based on the detected differences in energy expenditure, physical activity and adipose tissue weights, the results suggested that C5aR might play a role (either direct or indirect) in adipose, muscle and liver metabolism. Accordingly, C5aR gene expression was evaluated in the WT mice fed a CHOW or DIO diet. Expression was identified in gonadal adipose, muscle and liver tissues (Fig 3 A, B and C), where DIO diet fed WT mice showed a higher expression of C5aR vs CHOW diet fed WT mice for all three tissues. In addition, C5L2 expression was also evaluated in WT and C5aRKO mice on both diets (Fig 3 D-F). We observed a striking lowering of C5L2 expression in the muscle of C5aRKO mice compared to their WT counterpart (Fig 3E), with a smaller effect in adipose tissue (3D), but no difference in C5L2 expression in liver tissue (Fig 3F).


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)

C5aR and C5L2 expression in adipose, muscle and liver of mice.C5aR mRNA expression for WT CHOW (open bars) and WT diet-induced obesity (DIO) (checkered bars) for (A) gonadal adipose tissue, (B) quadriceps muscle, and (C) liver were measured. C5L2 mRNA expression for WT CHOW (open bars), WT DIO (checkered bars), KO CHOW (black bars) and KO DIO (striped bars) for (D) gonadal adipose tissue, (E) quadriceps muscle, and (F) liver were evaluated. Results are expressed as means ± SEM; n = 9–12 per group. Statistical differences were determined by t-test, for C5aRKO vs WT on their respective diets where *P<0.05, **P<0.001 and ***P<0.0001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3646841&req=5

pone-0062531-g003: C5aR and C5L2 expression in adipose, muscle and liver of mice.C5aR mRNA expression for WT CHOW (open bars) and WT diet-induced obesity (DIO) (checkered bars) for (A) gonadal adipose tissue, (B) quadriceps muscle, and (C) liver were measured. C5L2 mRNA expression for WT CHOW (open bars), WT DIO (checkered bars), KO CHOW (black bars) and KO DIO (striped bars) for (D) gonadal adipose tissue, (E) quadriceps muscle, and (F) liver were evaluated. Results are expressed as means ± SEM; n = 9–12 per group. Statistical differences were determined by t-test, for C5aRKO vs WT on their respective diets where *P<0.05, **P<0.001 and ***P<0.0001.
Mentions: Although C5a-C5aR functions have been largely investigated from the perspective of an immune response, based on the detected differences in energy expenditure, physical activity and adipose tissue weights, the results suggested that C5aR might play a role (either direct or indirect) in adipose, muscle and liver metabolism. Accordingly, C5aR gene expression was evaluated in the WT mice fed a CHOW or DIO diet. Expression was identified in gonadal adipose, muscle and liver tissues (Fig 3 A, B and C), where DIO diet fed WT mice showed a higher expression of C5aR vs CHOW diet fed WT mice for all three tissues. In addition, C5L2 expression was also evaluated in WT and C5aRKO mice on both diets (Fig 3 D-F). We observed a striking lowering of C5L2 expression in the muscle of C5aRKO mice compared to their WT counterpart (Fig 3E), with a smaller effect in adipose tissue (3D), but no difference in C5L2 expression in liver tissue (Fig 3F).

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