title: C5a receptor deficiency alters energy utilization and fat storage.
abstract: OBJECTIVE
  To investigate the impact of whole body C5a receptor (C5aR) deficiency on energy metabolism and fat storage.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Québec, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Roy
authors.forename: Abhishek
authors.initials: A
authors.lastname: Gupta
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fisette
authors.forename: Marc
authors.initials: M
authors.lastname: Lapointe
authors.forename: Pegah
authors.initials: P
authors.lastname: Poursharifi
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
authors.forename: Huiling
authors.initials: H
authors.lastname: Lu
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Norma
authors.initials: N
authors.lastname: Gerard
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000172:deficiency* / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics
chemical_list: C000594938:C5ar2 protein, mouse; D007328:Insulin; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D010100:Oxygen