Pan-PPAR agonist beneficial effects in overweight mice fed a high-fat high-sucrose diet.
OBJECTIVE
We analyzed the effect of peroxisome proliferator-activated receptor (PPAR) agonists on adipose tissue morphology, adiponectin expression, and its relation to glucose and insulin levels in C57BL/6 mice fed a high-fat high-sucrose (HFHS) diet.


METHODS
Male C57BL/6 mice received one of five diets: standard chow, HFHS chow, or HFHS plus rosiglitazone (PPAR-gamma agonist), fenofibrate (PPAR-alpha agonist), or bezafibrate (pan-PPAR agonist). Diets were administered for 11 wk and medications from week 6 to week 11. Glucose intolerance (GI) and insulin resistance were evaluated by oral glucose tolerance testing and homeostasis model assessment for insulin resistance, respectively. Adipocyte diameter was analyzed in epididymal, inguinal, and retroperitoneal fat pads and by adiponectin immunostain.


RESULTS
Mice fed the HFHS chow had hyperglycemia, GI, insulin resistance, increased fat pad weight, adipocyte hypertrophy, and decreased adiponectin immunostaining. Rosiglitazone improved GI, insulin sensitiveness, and adiponectin immunostaining, but it resulted in body weight gain, hyperphagia, and adipocyte and heart hypertrophy. Fenofibrate improved all parameters except for fasting glucose and GI. Bezafibrate was the most efficient in decreasing body weight and glucose intolerance.


CONCLUSIONS
Activation of PPAR-alpha, -delta, and -gamma together is better than the activation of PPAR-alpha or -gamma alone, because bezafibrate showed a wider range of action on metabolic, morphologic, and biometric alterations due to an HFHS diet in mice.
Fernandes-Santos
Caroline
C
Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
Carneiro
Rafael Evangelista
RE
de Souza Mendonca
Leonardo
L
Aguila
Marcia Barbosa
MB
Mandarim-de-Lacerda
Carlos Alberto
CA
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001629:Bezafibrate / Q000009:adverse effects / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D011345:Fenofibrate / Q000009:adverse effects / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006321:Heart / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050177:Overweight / Q000188:drug therapy*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D000077154:Rosiglitazone; D013395:Sucrose / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology
D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D019422:Dietary Sucrose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013395:Sucrose; D002784:Cholesterol; D011345:Fenofibrate; D001629:Bezafibrate