Induction of heme-oxygenase-1 (HO-1) does not enhance adiponectin production in human adipocytes: Evidence against a direct HO-1 – Adiponectin axis

• Inducers of HO-1 acutely (24–48 h) increase HO-1 mRNA, protein and activity.
• Acute induction of HO-1 does not enhance or rescue adiponectin production in healthy or TNFα-treated cells.
• Acute induction of HO-1 does not ameliorate TNFα-stimulated expression and secretion of pro-inflammatory adipocytokines.

Adiponectin is a salutary adipokine and hypoadiponectinemia is implicated in the aetiology of obesity-related inflammation and cardiometabolic disease making therapeutic strategies to increase adiponectin attractive. Emerging evidence, predominantly from preclinical studies, suggests induction of heme-oxygenase-1 (HO-1) increases adiponectin production and reduces inflammatory tone. Here, we aimed to test whether induction of HO-1 enhanced adiponectin production from mature adipocytes. Treatment of human adipocytes with cobalt protoporphyrin (CoPP) or hemin for 24–48 h increased HO-1 expression and activity without affecting adiponectin expression and secretion. Treatment of adipocytes with TNFα reduced adiponectin secretion and increased expression and secretion of additional pro-inflammatory cytokines, IL-6 and MCP-1, as well as expression of sXBP-1, a marker of ER stress. HO-1 induction failed to reverse these effects. These results demonstrate that induction of HO-1 does not directly enhance adiponectin production or ameliorate the pro-inflammatory effects of TNFα and argue against a direct HO-1 – adiponectin axis.