L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice.
We hypothesized that the apolipoprotein mimetic peptide L-4F, which induces arterial anti-oxidative enzymes and is vasoprotective in a rat model of diabetes, would ameliorate insulin resistance and diabetes in obese mice. L-4F (2 mg/kg/d) administered to ob/ob mice for 6 weeks limited weight gain without altering food intake, decreased visceral (P < 0.02) and subcutaneous (P < 0.045) fat content, decreased plasma IL-1beta and IL-6 levels (P < 0.05) and increased insulin sensitivity, resulting in decreased glucose (P < 0.001) and insulin (P < 0.036) levels. In addition, L-4F treatment increased aortic and bone marrow heme oxygenase (HO) activity and decreased aortic and bone marrow superoxide production (P < 0.001). L-4F treatment increased serum adiponectin levels (P < 0.037) and decreased adipogenesis in mouse bone marrow (P < 0.039) and in cultures of human bone marrow-derived mesenchymal stem cells (P < 0.022). This was manifested by reduced adiposity, improved insulin sensitivity, improved glucose tolerance, increased plasma adiponectin levels, and reduced IL-1beta and IL-6 levels in obese mice. This study highlights the existence of a temporal relationship between HO-1 and adiponectin that is positively affected by L-4F in the ob/ob mouse model of diabetes, resulting in the amelioration of the deleterious effects of diabetes.
Peterson
Stephen J
SJ
Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
Drummond
George
G
Kim
Dong Hyun
DH
Li
Ming
M
Kruger
Adam L
AL
Ikehara
Susumu
S
Abraham
Nader G
NG
D017667:Adipocytes / Q000187:drug effects*; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001011:Aorta / Q000201:enzymology; D016632:Apolipoprotein A-I / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D018716:Molecular Mimicry; D009765:Obesity / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*
D052242:Adiponectin; C499919:Adipoq protein, mouse; D016632:Apolipoprotein A-I; D001786:Blood Glucose; D007328:Insulin; D053583:Interleukin-1beta; D015850:Interleukin-6; C472885:L-4F peptide; D010455:Peptides; D051547:Heme Oxygenase-1