Artemisia extracts activate PPARγ, promote adipogenesis, and enhance insulin sensitivity in adipose tissue of obese mice

OBJECTIVE: Studies have shown that the inability of adipose tissue to properly expand during the obese state or respond to insulin can lead to metabolic dysfunction. Artemisia is a diverse group of plants that has a history of medicinal use. This study examines the ability of ethanolic extracts of Artemisia scoparia (SCO) and Artemisia santolinifolia (SAN) to modulate adipocyte development in cultured adipocytes and white adipose tissue (WAT) function in vivo using a mouse model of diet-induced obesity. RESEARCH DESIGN & PROCEDURES: Adipogenesis was assessed using Oil Red O staining and immunoblotting. A nuclear receptor specificity assay was used to examine the specificity of SCO- and SAN-induced PPARγ activation. C57BL/6J mice, fed a high-fat diet, were gavaged with saline, SCO, or SAN for 2 weeks. Whole-body insulin sensitivity was examined using insulin tolerance tests. WAT depots were assessed via immunoblotting for markers of insulin action and adipokine production. RESULTS: We established that SCO and SAN were highly specific activators of PPARγ and did not activate other nuclear receptors. After a one-week daily gavage, SCO- and SAN-treated mice had lower insulin-induced glucose disposal rates than control mice. At the end of the 2-week treatment period, SCO- and SAN-treated mice had enhanced insulin-responsive Akt serine-473 phosphorylation and significantly decreased MCP-1 levels in visceral WAT relative to control mice; these differences were depot specific. Moreover, plasma adiponectin levels were increased following SCO treatment. CONCLUSION: Overall, these studies demonstrate that extracts from two Artemisia species can have metabolically favorable effects on adipocytes and WAT

Cell-Type-Specific Type I Interferon Antagonism Influences Organ Tropism of Murine Coronavirus▿

Previous studies have demonstrated that mouse hepatitis virus (MHV) hepatotropism is determined largely by postentry events rather than by availability of the viral receptor. In addition, mutation of MHV nonstructural protein 2 (ns2) abrogates the ability of the virus to replicate in the liver and induce hepatitis but does not affect replication in the central nervous system (CNS). Here we show that replication of ns2 mutant viruses is attenuated in bone marrow-derived macrophages (BMM) generated from wild-type (wt) mice but not in L2 fibroblasts, primary astrocytes, or BMM generated from type I interferon receptor-deficient (IFNAR−/−) mice. In addition, ns2 mutants are more sensitive than wt virus to pretreatment of BMM, but not L2 fibroblasts or primary astrocytes, with alpha/beta interferon (IFN-α/β). The ns2 mutants induced similar levels of IFN-α/β in wt and IFNAR−/− BMM, indicating that ns2 expression has no effect on the induction of IFN but rather that it antagonizes a later step in IFN signaling. Consistent with these in vitro data, the virulence of ns2 mutants increased to near that of wt virus after depletion of macrophages in vivo. These data imply that the ability of MHV to replicate in macrophages is a prerequisite for replication in the liver and induction of hepatitis but not for replication or disease in the CNS, underscoring the importance of IFN signaling in macrophages in vivo for protection of the host from hepatitis. Our results further support the notion that viral tissue tropism is determined in part by postentry events, including the early type I interferon response