Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

We hypothesized that the induction of heme oxygenase (HO)-1 and increased HO activity, which induces arterial antioxidative enzymes and vasoprotection in a mouse and a rat model of diabetes, would ameliorate insulin resistance, obesity, and diabetes in the ob mouse model of type 2 diabetes. Lean and ob mice were intraperitoneally administered the HO-1 inducer cobalt protoporphyrin (3 mg/kg CoPP) with and without the HO inhibitor stannous mesoporphyrin (2 mg/100 g SnMP) once a week for 6 weeks. Body weight, blood glucose, and serum cytokines and adiponectin were measured. Aorta, adipose tissue, bone marrow, and mesenchymal stem cells (MSCs) were isolated and assessed for HO expression and adipogenesis. HO activity was reduced in ob mice compared with age-matched lean mice. Administration of CoPP caused a sustained increase in HO-1 protein, prevented weight gain, decreased visceral and subcutaneous fat content (P < 0.03 and 0.01, respectively, compared with vehicle animals), increased serum adiponectin, and decreased plasma tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-1beta levels (P < 0.05). HO-1 induction improved insulin sensitivity and glucose tolerance and decreased insulin levels. Upregulation of HO-1 decreased adipogenesis in bone marrow in vivo and in cultured MSCs and increased adiponectin levels in the culture media. Inhibition of HO activity decr

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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