Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice.
Increases in visceral fat are associated with increased inflammation, dyslipidemia, insulin resistance, glucose intolerance, and vascular dysfunction. We examined the effect of the potent heme oxygenase (HO)-1 inducer, cobalt protoporphyrin (CoPP), on regulation of adiposity and glucose levels in both female and male obese mice. Both lean and obese mice were administered CoPP intraperitoneally (3 mg/kg once per week) for 6 weeks. Serum levels of adiponectin, tumor necrosis factor α (TNFa), interleukin (IL)-1β and IL-6, and HO-1, PPARγ, pAKT, and pAMPK protein expression in adipocytes and vascular tissue were measured. While female obese mice continued to gain weight at a rate similar to controls, induction of HO-1 slowed the rate of weight gain in male obese mice. HO-1 induction led to lowered blood pressure levels in obese male and female mice similar to that of lean male and female mice. HO-1 induction also produced a significant decrease in the plasma levels of IL-6, TNFα, IL-1β, and fasting glucose of obese females compared to untreated female obese mice. HO-1 induction increased the number and decreased the size of adipocytes of obese animals. HO-1 induction increased adiponectin, pAKT, pAMPK, and PPARγ levels in adipocyte of obese animals. Induction of HO-1 in adipocytes was associated with an increase in adiponectin and a reduction in inflammatory cytokines. These findings offer the possibility of treating not only hypertension, but also other detrimental metabolic consequences of obesity including insulin resistance and dyslipidemia in obese populations by induction of HO-1 in adipocytes.
Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Angela
A
Burgess
Ming
M
Li
Luca
L
Vanella
Dong Hyun
DH
Kim
Rita
R
Rezzani
Luigi
L
Rodella
Komal
K
Sodhi
Martina
M
Canestraro
Pavel
P
Martasek
Stephen J
SJ
Peterson
Attallah
A
Kappas
Nader G
NG
Abraham
D055372:AMP-Activated Protein Kinases / Q000032:analysis; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology*; D052242:Adiponectin / Q000097:blood; D050154:Adiposity; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology*; D047495:PPAR gamma / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D011524:Protoporphyrins / Q000494:pharmacology*; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
D052242:Adiponectin; D001786:Blood Glucose; D053583:Interleukin-1beta; D015850:Interleukin-6; D047495:PPAR gamma; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases