A PPAR Pan Agonist, MHY2013 Alleviates Age-Related Hepatic Lipid Accumulation by Promoting Fatty Acid Oxidation and Suppressing Inflammation

An, Hye Jin; Lee, Bonggi; Kim, Sang Woo; Kim, Dae Hyun; Chung, Ki Wung; Ha, Su Gyeong; Park, Kyung Chul; Park, Yeo Jin; Kim, Seong‐Jin; Yun, Hwi Young; Chun, Pusoon; Yu, Byung Pal; Moon, Hyung Ryong; Chung, Hae Young

doi:10.1248/bpb.b17-00371

Cited by 22 publications

(14 citation statements)

References 25 publications

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“…A previous study demonstrated that peroxisomal function was inversely correlated with aging [36]. Reduced ACOX1 expression and peroxisomal fatty acid β-oxidation activity have been observed in the liver of old rats [37]. In another study, Sanguino et al [38] revealed that aging strongly decreases the activity and expression of PPARα in rat liver.…”

Section: Hfd-mediated Oxidative Stressmentioning

confidence: 99%

Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function

2019

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Cognitive dysfunction is linked to chronic low-grade inflammatory stress that contributes to cell-mediated immunity in creating an oxidative environment. Food is a vitally important energy source; it affects brain function and provides direct energy. Several studies have indicated that high-fat consumption causes overproduction of circulating free fatty acids and systemic inflammation. Immune cells, free fatty acids, and circulating cytokines reach the hypothalamus and initiate local inflammation through processes such as microglial proliferation. Therefore, the role of high-fat diet (HFD) in promoting oxidative stress and neurodegeneration is worthy of further discussion. Of particular interest in this article, we highlight the associations and molecular mechanisms of HFD in the modulation of inflammation and cognitive deficits. Taken together, a better understanding of the role of oxidative stress in cognitive impairment following HFD consumption would provide a useful approach for the prevention of cognitive dysfunction.

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Section: Hfd-mediated Oxidative Stressmentioning

confidence: 99%

Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function

2019

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“…MHY2013 is another PPAR pan-agonist that also activates all three PPAR isotypes. In aged Sprague-Dawley (SD) rats, MHY2013 treatment improved age-related hepatic lipid accumulation, and resulted in upregulated β-oxidation signaling and lower inflammation in the liver [ 162 ]. The PPAR pan-agonist Lanifibranor (CAS ID 927961-18-0) is reportedly effective in experimental skin and lung fibrosis [ 163 , 164 ].…”

Section: Pharmacological Strategies Targeting Pparβ/δ For Nafld Trmentioning

confidence: 99%

Insights into the Role of PPARβ/δ in NAFLD

Chen

Montagner

Tan

et al. 2018

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is a major health issue in developed countries. Although usually associated with obesity, NAFLD is also diagnosed in individuals with low body mass index (BMI) values, especially in Asia. NAFLD can progress from steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by liver damage and inflammation, leading to cirrhosis and hepatocellular carcinoma (HCC). NAFLD development can be induced by lipid metabolism alterations; imbalances of pro- and anti-inflammatory molecules; and changes in various other factors, such as gut nutrient-derived signals and adipokines. Obesity-related metabolic disorders may be improved by activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)β/δ, which is involved in metabolic processes and other functions. This review is focused on research findings related to PPARβ/δ-mediated regulation of hepatic lipid and glucose metabolism and NAFLD development. It also discusses the potential use of pharmacological PPARβ/δ activation for NAFLD treatment.

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“…The development of PPARα/γ/δ pan agonists as anti-diabetic, anti-obesity, or hypolipidemic drugs is still actively ongoing 74 , 75 . For example, IVA 337 is a potent and well-balanced pan PPAR agonist which showed promising results in vitro and in vivo and is expected to be used to treat patients with metabolic syndrome and non-alcoholic steatohepatitis 76 .…”

Section: Other Pparγ Modulators and Agonistsmentioning

confidence: 99%

Re-highlighting the action of PPARγ in treating metabolic diseases

2018

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Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor family and plays an important role in adipocyte differentiation, glucose homeostasis, and insulin sensitivity. Thiazolidinediones (TZDs), synthetic ligands of PPARγ, have been used for the treatment of diabetes mellitus for two decades. TZDs were expected to be amazing drugs not only for type 2 diabetes but also for metabolic syndrome and atherosclerotic vascular disease because they can reduce both insulin resistance and inflammation in experimental studies. However, serious unwanted effects pushed TZDs back to an optional second-tier drug for type 2 diabetes. Nevertheless, PPARγ is still one of the most important targets for the treatment of insulin resistance and diabetes mellitus, and novel strategies to modulate PPARγ activity to enhance its beneficial effects and reduce unwanted adverse effects are anticipated. Recent studies showed that post-translational modification (PTM) of PPARγ regulates PPARγ activity or stability and may be a novel way to optimize PPARγ activity with reduced adverse effects. In this review, we will focus on recent advances in PTM of PPARγ and the mechanisms regulating PPARγ function as well as in the development of PPARγ modulators or agonists.

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A PPAR Pan Agonist, MHY2013 Alleviates Age-Related Hepatic Lipid Accumulation by Promoting Fatty Acid Oxidation and Suppressing Inflammation

Cited by 22 publications

References 25 publications

Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function

Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function

Insights into the Role of PPARβ/δ in NAFLD

Re-highlighting the action of PPARγ in treating metabolic diseases

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