Abstract

BackgroundFailure of adipocytes to expand during periods of energy excess can result in undesirable metabolic consequences such as ectopic fat accumulation and insulin resistance. Blinded screening studies have indicated that Artemisia scoparia (SCO) extracts can enhance adipocyte differentiation and lipid accumulation in cultured adipocytes. The present study tested the hypothesis that SCO treatment modulates fat cell development and function in vitro and insulin sensitivity in adipose tissue in vivo.Methods In vitro experiments utilized a Gal4-PPARγ ligand binding domain (LBD) fusion protein-luciferase reporter assay to examine PPARγ activation. To investigate the ability of SCO to modulate adipogenesis and mature fat cell function in 3T3-L1 cells, neutral lipid accumulation, gene expression, and protein secretion were measured by Oil Red O staining, qRT-PCR, and immunoblotting, respectively. For the in vivo experiments, diet-induced obese (DIO) C57BL/6J mice were fed a high-fat diet (HFD) or HFD containing 1% w/w SCO for four weeks. Body weight and composition, food intake, and fasting glucose and insulin levels were measured. Phospho-activation and expression of insulin-sensitizing proteins in epididymal adipose tissue (eWAT) were measured by immunoblotting.ResultsEthanolic extracts of A. scoparia significantly activated the PPARγ LBD and enhanced lipid accumulation in differentiating 3T3-L1 cells. SCO increased the transcription of several PPARγ target genes in differentiating 3T3-L1 cells and rescued the negative effects of tumor necrosis factor α on production and secretion of adiponectin and monocyte chemoattractant protein-1 in fully differentiated fat cells. DIO mice treated with SCO had elevated adiponectin levels and increased phosphorylation of AMPKα in eWAT when compared to control mice. In SCO-treated mice, these changes were also associated with decreased fasting insulin and glucose levels.ConclusionSCO has metabolically beneficial effects on adipocytes in vitro and adipose tissue in vivo, highlighting its potential as a metabolically favorable botanical supplement.

Highlights

  • Adipocytes have long been recognized as storage sites for excess energy

  • Since our initial findings indicated that SCO promotes adipogenesis, we examined the ability of SCO to modulate fat cell development and function in vitro and insulin sensitivity in adipose tissue in vivo

  • Our results indicate that SCO increases the transcription of several peroxisome proliferator activated receptor gamma (PPARc) target genes in differentiating 3T3-L1 cells and rescues the negative effects of tumor necrosis factor a (TNFa) on adipocyte secretion of adiponectin (ADPN) and monocyte chemoattractant protein-1 (MCP-1)

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Summary

Introduction

Adipocytes have long been recognized as storage sites for excess energy. A growing body of evidence has demonstrated that adipose tissue can act as an endocrine organ and functions as an important regulator of whole-body energy homeostasis. Evidence has since emerged demonstrating that disruption of adipocyte differentiation and/or expansion is maladaptive and leads to ectopic fat accumulation and metabolic dysfunction, including insulin resistance and T2DM [4,5]. Increased adipocyte turnover due to an elevated rate of cell death can be associated with obesity [6] These findings favor an alternative hypothesis that adipose tissue expansion associated with increased adipogenesis results in adipocytes with beneficial endocrine functions that contribute to an improved metabolic status during obesity. Failure of adipocytes to expand during periods of energy excess can result in undesirable metabolic consequences such as ectopic fat accumulation and insulin resistance. The present study tested the hypothesis that SCO treatment modulates fat cell development and function in vitro and insulin sensitivity in adipose tissue in vivo

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