The 1α,25(OH) 2 D 3 Analogs ZK159222 and ZK191784 Show Anti-Inflammatory Properties in Macrophage-Induced Preadipocytes via Modulating the NF-κB and MAPK Signaling

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)

Purpose Key research findings suggest that attenuating metaflammation in adipose tissue might be a strategic step to prevent the metabolic syndrome and its associated disease outcomes. The anti-inflammatory effects of 1α,25(OH) 2 D 3 have been confirmed in our previous studies, but adverse effects induced at high concentrations restrict its potential clinical translation. Two synthetic 1α,25(OH) 2 D 3 analogs ZK159222 and ZK191784 have manifested promising tissue-specific immunomodulatory actions, but limited data are available on adipose tissue. Hence, in this study, we investigated whether ZK159222 and ZK191784 act on preadipocytes or macrophages to attenuate metaflammatory responses via modulating inflammatory and metabolic signaling in macrophage-induced preadipocytes. Methods Preadipocyte-specific effects of ZK159222 and ZK191784 on macrophage-induced preadipocytes were tested by pre-incubating and incubating preadipocytes with the analogs and MacCM. Separately, macrophage-specific effects of both analogs on macrophage-induced preadipocytes were tested by incubating preadipocytes with analog-MacCM or MacCM. The effects of 1α,25(OH) 2 D 3 were also examined and set as the positive control. Metaflammatory responses were determined as the concentrations and gene expression of major pro-inflammatory cytokines including IL-1β, IL-6, IL-8, MCP-1 and RANTES, measured using ELISA

Evidence level

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

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