Abstract
BackgroundTo investigate the potential of Catharanthus roseus leaf aqueous crude extract (CRACE) as a regulator of adipocyte development and function.Methods3T3-L1 adipogenesis model was used to investigate the effect of CRACE on adipogenesis. 3T3-L1 preadipocytes (for adipogenic differentiation) and mature 3T3-L1 adipocytes (for adipocyte function) were treated with non-toxic doses of CRACE. The outcomes were corroborated by intracellular lipid accumulation, expression of pro-and anti-adipogenic effector molecules. To investigate CRACE mediated lipolysis, cAMP accumulation, glycerol release and phosphorylation of key effector molecules were tested in treated mature adipocytes. Finally, the extract was fractionated to identify the active molecule/s in the extract.ResultsCRACE significantly reduced adipocyte differentiation by modulating PPARγ expression. At early stage CRACE directly targeted Lipin1 expression and consequently impacted KLF7, subsequently expression of GATA2, CEBPα, SREBP1c were targeted, with PPARγ expression, particularly curtailed. While CRACE significantly reduced several lipogenic genes like FAS and GPD1 in mature adipocytes, concomitantly, it greatly increased lipolysis resulting in decreased lipid accumulation in mature adipocytes. The increase in lipolysis was due to decreased Akt activation, increased cAMP level, and PKA activity. The fractionation of CRACE allowed identification of two fractions with potent anti-adipogenic activity. Both the fractions contained 1α, 25-dihydroxy Vitamin D3 as major component.Conclusions1α, 25-dihydroxy Vitamin D3 containing CRACE can be developed into an effective anti-obesity formulation that decreases adipogenesis and increases lipid catabolism.
Highlights
To investigate the potential of Catharanthus roseus leaf aqueous crude extract (CRACE) as a regulator of adipocyte development and function
CRACE reduced lipid accumulation in differentiating 3T3L1 cells Prior to test the effect of CRACE on adipocyte differentiation, nontoxic dose of the extract was determined by CRACE modulated expression of early and late adipogenic regulators To understand the mechanism of CRACE mediated Peroxisome proliferative activated receptor γ (PPARγ) downregulation, mRNA expression of key transcription regulators of PPARγ gene were
Top panel represents the design of the experiment. 3T3-L1 cells were induced with adipogenic cocktail ± CRACE at the displayed doses for 4 days and subsequently kept in maintenance medium for an additional 4 days
Summary
To investigate the potential of Catharanthus roseus leaf aqueous crude extract (CRACE) as a regulator of adipocyte development and function. Function and its microenvironment have become potential caches to counter health issues like obesity, cardiovascular disease, type diabetes, cancer and many more metabolic as well as physiological disturbances [1, 2]. Dysregulations of adipogenesis leads to adverse repercussions like excessive accumulation of triacylglycerol (TAG) in adipocytes (hypertrophy) and increase in the number of adipocytes (hyperplasia). Both conditions contribute to obesity; which eventually changes the tissue microenvironment, leading to recruitment of pro-inflammatory macrophages, heightened inflammation and insulin resistance [5,6,7]. It is necessary to search for new therapeutic agents to treat obesity, which has acquired the status of a global epidemic
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