Expression pattern of thermogenesis-related factors in interscapular brown adipose tissue of alloxan-treated rats: beneficial effect of L-arginine.
Metabolic abnormalities underlying diabetes can be abrogated by L-arginine. Here we examined the molecular basis of disturbed interscapular brown adipose tissue (IBAT) thermogenesis and the possible role of nitric oxide (NO) in the IBAT of diabetic rats. To induce diabetes, adult Mill Hill hybrid hooded male rats were given a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided into three subgroups receiving: (i) L-arginine.HCl (2.25%) or (ii) N(omega)-nitro-L-arginine methyl ester (L-NAME.HCl, 0.01%) for 12 days in drinking water and (iii) untreated controls. Treatment of the diabetic animals started after diabetes induction (glucose level 12 mmol/L). Diabetes led to a decrease in the mRNA levels of uncoupling protein 1 (UCP1), peroxisomal proliferator activator receptor gamma (PPARgamma) and endothelial NO synthase (eNOS) as revealed by RT-PCR. The diabetic rats had reduced eNOS and inducible NOS (iNOS) protein contents accompanied by low tissue vascularization, a parameter directly related to tissue thermogenic state. Downregulation of glutathione peroxidase (GSH-Px) and catalase (CAT) transcripts were also observed in diabetes. In contrast, the expression level of PPARgamma coactivator-1alpha (PGC-1alpha) mRNA was elevated. Supplementation with L-arginine not only restored diabetes-induced changes in the expressions of these molecules important for IBAT regulation, but also increased the vascularity. Interestingly, L-NAME induced similar patterns of changes in vascularity and PGC-1alpha mRNA level as did l-arginine. In summary, our results provide insight into the molecular basis underlying diabetes-induced metabolic and functional disturbances in the IBAT and suggest a beneficial role for the L-arginine-NO production pathway.
Vasilijević
A
A
Department of Physiology, Institute for Biological Research, Sinisa Stanković, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Vojcić
Lj
Lj
Dinulović
I
I
Buzadzić
B
B
Korać
A
A
Petrović
V
V
Janković
A
A
Korać
B
B
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism*; D000496:Alloxan; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology*; D001415:Back; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012039:Regional Blood Flow; D022722:Thermogenesis / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1
D000975:Antioxidants; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D000496:Alloxan; D001120:Arginine; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat