Shikonin protects against obesity through the modulation of adipogenesis, lipogenesis, and β-oxidation in vivo

Gwon, So Young; Choi, Won Hee; Lee, Da Hye; Ahn, Ji Yun; Jung, Chang Hwa; Moon, BoKyung; Ha, Tae Youl

doi:10.1016/j.jff.2015.04.040

Cited by 22 publications

(16 citation statements)

References 44 publications

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“…Several reports have indicated PPAR-γ , C/EBP-α , and aP2 are the major transcriptional genes related to adipogenesis and lipogenesis genes, such as FAS and SCD-1 . PPAR-γ is considered the major regulator of adipocyte differentiation and, along with C/EBP-α , it regulates the expression of downstream target genes [ 13 , 19 , 32 ]. We performed RT-PCR to analyze the molecular metabolism of VDAE-mediated adipogenesis and lipogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…[ 9 , 10 , 11 , 12 ]. Moreover, regulation of the production of lipogenic enzymes, such as lipoprotein lipase (LPL), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and fatty acid esterification transcriptional factors, such as stearoyl-CoA desaturase (SCD-1), is important in the process of lipogenesis in adipose and hepatic tissues [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Obesity Effect of the Above-Ground Part of Valeriana dageletiana Nakai ex F. Maek Extract in High-Fat Diet-Induced Obese C57BL/6N Mice

et al. 2017

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Valeriana dageletiana Nakai ex F. Maek (VD) has been used as traditional medicine for the treatment of restlessness and sleeping disorders. However, it is still unclear whether obesity in mice can be altered by diet supplementation with VD. In this study, we first investigated the influences of VD on the accumulation of lipid content in 3T3-L1 cells; and the results showed that the above-ground VD extracts (VDAE) suppressed the differentiation of 3T3-L1 preadipocytes in a concentration-dependent manner without cytotoxicity. Thus, the effects of VDAE on preventing obesity were then studied in the C57BL/6N mice for 10 weeks (n = 6): normal-fat diet, high-fat diet (HFD), HFD supplemented with 1% (10 g/kg) Garcinia combogia extract (positive control), and HFD supplemented with 1% (10 g/kg) VDAE. The results showed that VDAE reduced food efficiency ratio, body weight, epididymal adipose and hepatic tissue weight, hepatic lipid metabolites, and triacylglycerol and cholesterol serum levels compared to the high-fat diet group. Moreover, VD significantly inhibited the expression of adipogenic genes, such as PPAR-γ, C/EBP-α, and aP2, and lipogenic genes, such as SREBP-1c, FAS, SCD-1, and CD36, in epididymal adipose tissue and hepatic tissue. These findings indicate anti-adipogenic and anti-lipogenic effects of VDAE and suggest that it could be a potent functional food ingredient for the prevention of high-fat diet-induced obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Obesity Effect of the Above-Ground Part of Valeriana dageletiana Nakai ex F. Maek Extract in High-Fat Diet-Induced Obese C57BL/6N Mice

et al. 2017

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“…Several studies have reported that shikonin can effectively ameliorate obesity and hepatic fibrosis [23][24][25]. We previously demonstrated the anti-obesity effect of shikonin by inhibiting adipogenesis and lipogenesis and increasing β-oxidation [18,19]. Shikonin also attenuated liver fibrosis by downregulating the transforming growth factor-β1/Smads pathway and by inhibiting autophagy [31].…”

Section: Discussionmentioning

confidence: 97%

“…Previous studies have demonstrated that shikonin exhibits anti-inflammatory [14] and anti-cancer effects [15,16]. Many studies have shown that shikonin can exert protective effects against obesity by modulating glucose tolerance, lipogenesis and β-oxidation [17][18][19]. Recent studies have shown that shikonin plays a significant role on AMPK activation against adipogenesis, diabetes, hepatic carcinoma and hepatic fibrosis [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Shikonin Attenuates Hepatic Steatosis by Enhancing Beta Oxidation and Energy Expenditure via AMPK Activation

et al. 2020

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Shikonin, a natural plant pigment, is known to have anti-obesity activity and to improve insulin sensitivity. This study aimed to examine the effect of shikonin on hepatic steatosis, focusing on the AMP-activated protein kinase (AMPK) and energy expenditure in Hepa 1-6 cells and in high-fat fed mice. Shikonin increased AMPK phosphorylation in a dose- and time-dependent manner, and inhibition of AMPK with compound C inhibited this activation. In an oleic acid-induced steatosis model in hepatocytes, shikonin suppressed oleic acid-induced lipid accumulation, increased AMPK phosphorylation, suppressed the expression of lipogenic genes, and stimulated fatty acid oxidation-related genes. Shikonin administration for four weeks decreased body weight gain and the accumulation of lipid droplets in the liver of high-fat fed mice. Furthermore, shikonin promoted energy expenditure by activating fatty acid oxidation. In addition, shikonin increased the expression of PPARγ coactivator-1α (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) and other mitochondrial function-related genes. These results suggest that shikonin attenuated a high fat diet-induced nonalcoholic fatty liver disease by stimulating fatty acid oxidation and energy expenditure via AMPK activation.

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“…Similarly, it remains unclear whether the anti-obesogenic and antidiabetic effects of shikonin are mediated through inhibition of PKM2; however, the health-promoting effects of shikonin may uncover novel roles of PKM2 in the pathogenesis of various metabolic and non-metabolic human diseases. Recent studies have shown that shikonin exerts protective effects against high fat diet-(HFD) induced obesity in mice [ 243 , 244 ] and rats [ 245 ]. Shikonin also alleviated HFD-induced hepatic lipid accumulation, enhanced β-oxidation and energy expenditure in mice [ 243 , 246 ], and prevented HFD-induced liver fibrosis in rats [ 247 ].…”

Section: Emerging Areas Of Research Involving Pkm2mentioning

confidence: 99%

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Puckett

Alquraishi

Chowanadisai

et al. 2021

IJMS

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Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.

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Shikonin protects against obesity through the modulation of adipogenesis, lipogenesis, and β-oxidation in vivo

Cited by 22 publications

References 44 publications

Anti-Obesity Effect of the Above-Ground Part of Valeriana dageletiana Nakai ex F. Maek Extract in High-Fat Diet-Induced Obese C57BL/6N Mice

Anti-Obesity Effect of the Above-Ground Part of Valeriana dageletiana Nakai ex F. Maek Extract in High-Fat Diet-Induced Obese C57BL/6N Mice

Shikonin Attenuates Hepatic Steatosis by Enhancing Beta Oxidation and Energy Expenditure via AMPK Activation

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

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