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  • Due to intense biological alterations induced by various ris

    2020-07-27

    Due to intense biological alterations induced by various risk factors of obesity, the adipose tissue undergoes adaptations such as adipocyte hypertrophy superimposed with hyperplasia (Jo et al., 2009). In addition to these changes, the adipocytes experience a process of cellular differentiation there by converting the pre adipocytes into lipid laden adipocytes resulting in increased fat mass (Tang and Lane, 2012). Moreover, obesity is considered to be the cause as well as consequence of insulin resistance a crucial component of metabolic syndrome. Inevitably these very facts indicate advantage of targeting adipocyte differentiation for management of obesity and its associated metabolic complications (Moseti et al., 2016). Adipogenic differentiation is orchestrated by a complex network of transcriptional factors that regulate the expression of multiple proteins which are crucial for the establishment of differentiated phenotypic adipocyte. The principal transcriptional factors that regulate adipocyte differentiation are the peroxisome proliferator activated receptor gamma (PPAR-γ), CCAT/enhancer binding protein alpha (C/EBPα) and sterol regulatory element binding protein-1c (SREBP-1c) (Fève, 2005, Ji et al., 2015). Amongst these regulators, PPAR-γ is widely expressed in the white adipose tissue and also modulates the lipid metabolism besides controlling adipocyte differentiation. The C/EBP-α is a leucine zipper family transcriptional factor and plays a vital role in induction of terminal differentiation (Rosen et al., 2002, Siersbæk et al., 2010). Finally, SREBP-1c is a major regulator of lipogenic proteins such as fatty chloroquine phosphate synthase (FAS) and its activity is under the control of insulin and AMP-activated protein kinase (AMPK) (Moseti et al., 2016). Constitutional activation of PPAR-γ in the absence of other transcription factors can trigger differentiation of immature fibroblasts to mature adipocyte there by establishing its central role in regulation of adipogenic differentiation (Wafer et al., 2017). AMPK is a conserved metabolic sensor of the cell, which is phosphorylated under stress super imposed by low energy states such as higher levels of AMP and ATP ratio. AMPK is activated by phosphorylation at Thr172 along with inhibition of dephosphorylation, this biological sequel leads to shut down of energy consuming anabolic processes and switches on the energy stemming catabolic processes (López and Tena-Sempere, 2017, Daval et al., 2006). Currently approved anti-obesity drugs for long term use such as orlistat, lorcaserin and liraglutide are efficient in reduction of weight gain but are limited in usage due to their adverse effect profile and higher cost (Krentz et al., 2016; Mopuri and Islam, 2017). In contrast to this, plant derived molecules produce comparatively insignificant quantum of adverse effects and are affordable making them suitable agents for management of obesity (Mukherjee et al., 2015, Mopuri and Islam, 2017). Herbal teas were used from ancient times for their medicinal properties, especially in disorders related to cardiovascular and metabolic functions (Ravikumar, 2014). Currently there is an enhanced interest in herbal teas as remedy for obesity and associated complications, flowers of Hibiscus rosa sinensis are chloroquine phosphate used widely for this purpose (Priya et al., 2016). Hibiscus rosa sinensis (Family: Malvaceae) an ornamental plant grown in India and China is known from ancient times for its medicinal properties. The major phytoconstituents reported in Hibiscus flowers are quercetin, cyanidin, thiamine, niacin, ascorbic acid, genistic acid, lauric acid, margaric acid, hentriacontane and calcium oxalate (Falade et al., 2009, Gomathi et al., 2008, Lim, 2014). It was popular in traditional medicine of various cultures as a wound healing agent, detoxifier, anti-fertility agent, anti hypertensive, hypolipidemic, anti-cancer agent, anti asthmatic agent and cardio-protective agent (Goldberg et al., 2016, Jadhav et al., 2015, Vincenta and Patel, 2016). Research findings reported wound healing, anti-fertility, anti hypertensive, hypolipidemic, anti asthmatic and cardio-protective properties of Hibiscus rosa sinensis (Afiune et al., 2017, Bhaskar and Nithya, 2012, Gauthaman et al., 2006, Gomathi et al., 2008, Khan et al., 2014, Pethe et al., 2017, Ruban and Gajalakshmi, 2012, Sachdewa and Khemani, 2003, Shewale et al., 2012). Despite the existence of reports on hypolipidemic potential of Hibiscus rosa sinensis flower extract, there exists a huge lacuna regarding the detailed mechanistic studies. Among various in vitro models for adipogenesis, mouse derived 3T3-L1 fibroblasts are well established and regularly used to study effect of compounds on adipogenic differentiation and characterizing their mechanism of action (Ruiz-Ojeda et al., 2016). In this scenario, the current investigation was designed to delineate possible molecular mechanism behind the lipid lowering effect of Hibiscus rosa sinensis using well established in vitro model of 3T3-L1 fibroblasts cells.