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

Oxygen consumption and locomotor activity.(A and B): Oxygen consumption after diet treatment for one week (A) and 12 weeks (B), evaluated over a 48 hour period for wildtype (WT, open circles) and C5aRKO mice (solid circles) on a high fat high sucrose diet-induced obesity (DIO) diet. (C): Respiration quotient (RQ) for the same 48 hour period for WT and C5aRKO mice on CHOW or DIO diet. (D): Total walking distance over the 48-hour period for WT and C5aRKO mice on CHOW or DIO diet. Results are presented as means ± SEM of n = 8 mice per group. For calorimetry results, “dark cycle” indicates the active period. Data were analysed by 2-way RM-ANOVA (A and B) and by ANOVA followed by t-test (C and D), where *P<0.05 for C5aRKO vs WT on their respective diets, unless otherwise indicated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646841&req=5

pone-0062531-g001: Oxygen consumption and locomotor activity.(A and B): Oxygen consumption after diet treatment for one week (A) and 12 weeks (B), evaluated over a 48 hour period for wildtype (WT, open circles) and C5aRKO mice (solid circles) on a high fat high sucrose diet-induced obesity (DIO) diet. (C): Respiration quotient (RQ) for the same 48 hour period for WT and C5aRKO mice on CHOW or DIO diet. (D): Total walking distance over the 48-hour period for WT and C5aRKO mice on CHOW or DIO diet. Results are presented as means ± SEM of n = 8 mice per group. For calorimetry results, “dark cycle” indicates the active period. Data were analysed by 2-way RM-ANOVA (A and B) and by ANOVA followed by t-test (C and D), where *P<0.05 for C5aRKO vs WT on their respective diets, unless otherwise indicated.

Mentions: Energy expenditure was measured with indirect calorimetry, using several parameters. After one week of DIO diet, as shown in Fig. 1A, O2 consumption was higher in C5aRKO mice compared to WT mice (p<0.001, 2way ANOVA). Over the 48-h period, this increase was present in both the dark cycle, when mice are known to initiate eating, and in the light (sleeping) cycle. There was no significant difference between KO and WT mice on CHOW diet (data not shown). Interestingly, the same results were observed after 12 weeks of the DIO diet, as shown in Fig. 1B, O2 consumption was increased over a 48-h period in C5aRKO mice compared to WT mice. Analysis of RQ, which is indicative of relative energy substrate usage (glucose vs. fatty acid), indicates that C5aRKO mice receiving a CHOW diet had a preference for glucose oxidation, as indicated by higher RQ compared with WT mice (Fig. 1C). On a DIO diet, RQ decreases, indicative of greater fat oxidation relative to glucose (Fig. 1C). Physical activity, evaluated as two components: cumulative walking distance and total activity, was also monitored during the time in the calorimetric chambers. Cumulative walking distance represents movement within the x-axis direction, whereas total activity accounts for movement within all three axes. Over the 48-h time period, C5aRKO mice walked less vs WT mice (Fig. 1D) regardless of CHOW or DIO diet, although there was no difference in total physical activity (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)

Oxygen consumption and locomotor activity.(A and B): Oxygen consumption after diet treatment for one week (A) and 12 weeks (B), evaluated over a 48 hour period for wildtype (WT, open circles) and C5aRKO mice (solid circles) on a high fat high sucrose diet-induced obesity (DIO) diet. (C): Respiration quotient (RQ) for the same 48 hour period for WT and C5aRKO mice on CHOW or DIO diet. (D): Total walking distance over the 48-hour period for WT and C5aRKO mice on CHOW or DIO diet. Results are presented as means ± SEM of n = 8 mice per group. For calorimetry results, “dark cycle” indicates the active period. Data were analysed by 2-way RM-ANOVA (A and B) and by ANOVA followed by t-test (C and D), where *P<0.05 for C5aRKO vs WT on their respective diets, unless otherwise indicated.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062531-g001: Oxygen consumption and locomotor activity.(A and B): Oxygen consumption after diet treatment for one week (A) and 12 weeks (B), evaluated over a 48 hour period for wildtype (WT, open circles) and C5aRKO mice (solid circles) on a high fat high sucrose diet-induced obesity (DIO) diet. (C): Respiration quotient (RQ) for the same 48 hour period for WT and C5aRKO mice on CHOW or DIO diet. (D): Total walking distance over the 48-hour period for WT and C5aRKO mice on CHOW or DIO diet. Results are presented as means ± SEM of n = 8 mice per group. For calorimetry results, “dark cycle” indicates the active period. Data were analysed by 2-way RM-ANOVA (A and B) and by ANOVA followed by t-test (C and D), where *P<0.05 for C5aRKO vs WT on their respective diets, unless otherwise indicated.
Mentions: Energy expenditure was measured with indirect calorimetry, using several parameters. After one week of DIO diet, as shown in Fig. 1A, O2 consumption was higher in C5aRKO mice compared to WT mice (p<0.001, 2way ANOVA). Over the 48-h period, this increase was present in both the dark cycle, when mice are known to initiate eating, and in the light (sleeping) cycle. There was no significant difference between KO and WT mice on CHOW diet (data not shown). Interestingly, the same results were observed after 12 weeks of the DIO diet, as shown in Fig. 1B, O2 consumption was increased over a 48-h period in C5aRKO mice compared to WT mice. Analysis of RQ, which is indicative of relative energy substrate usage (glucose vs. fatty acid), indicates that C5aRKO mice receiving a CHOW diet had a preference for glucose oxidation, as indicated by higher RQ compared with WT mice (Fig. 1C). On a DIO diet, RQ decreases, indicative of greater fat oxidation relative to glucose (Fig. 1C). Physical activity, evaluated as two components: cumulative walking distance and total activity, was also monitored during the time in the calorimetric chambers. Cumulative walking distance represents movement within the x-axis direction, whereas total activity accounts for movement within all three axes. Over the 48-h time period, C5aRKO mice walked less vs WT mice (Fig. 1D) regardless of CHOW or DIO diet, although there was no difference in total physical activity (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