Pivotal Roles of Peroxisome Proliferator-Activated Receptors (PPARs) and Their Signal Cascade for Cellular and Whole-Body Energy Homeostasis

Lamichane, Shreekrishna; Lamichane, Babita Dahal; Kwon, Sang‐Mo

doi:10.3390/ijms19040949

Cited by 109 publications

(92 citation statements)

References 78 publications

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“…According to the evidence, the activation of PPAR‐α stimulates the uptake, utilization, and catabolism of fatty acids through the upregulation of genes that are involved in fatty acid transport and mitochondrial, and peroxisomal fatty acid beta‐oxidation . Therefore, PPAR‐α activation appears to play an essential role in the modulation of obesity, mainly central obesity.…”

Section: Discussionmentioning

confidence: 99%

A systematic review of the effects of oleoylethanolamide, a high‐affinity endogenous ligand of PPAR‐α, on the management and prevention of obesity

Tutunchi

Saghafi-Asl

Ostadrahimi

2020

Clin Exp Pharma Physio

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Along with an increase in overweight and obesity among all age groups, the development of efficacious and safe anti‐obesity strategies for patients, as well as health systems, is critical. Oleoylethanolamide (OEA), a high‐affinity endogenous ligand of nuclear receptor peroxisome proliferator‐activated receptor alpha (PPAR‐α), plays important physiological and metabolic actions. OEA is derived from oleic acid, a monounsaturated fatty acid, which has beneficial effects on body composition and regional fat distribution. The role of OEA in the modulation of food consumption and weight management makes it an attractive molecule requiring further exploration in obesogenic environments. This systematic review was conducted to assess the effects of OEA on the obesity management, with emphasizing on its physiological roles and possible mechanisms of action in energy homeostasis. We searched PubMed/Medline, Google Scholar, ScienceDirect, Scopus, ProQuest, and EMBASE up until September 2019. Out of 712 records screened, 30 articles met the study criteria. The evidence reviewed here indicates that OEA, an endocannabinoid‐like compound, leads to satiation or meal termination through PPAR‐α activation and fatty acid translocase (FAT)/CD36. Additionally, the lipid‐amide OEA stimulates fatty acid uptake, lipolysis, and beta‐oxidation, and also promotes food intake control. OEA also exerts satiety‐inducing effects by activating the hedonic dopamine pathways and increasing homeostatic oxytocin and brain histamine. In conclusion, OEA may be a key component of the physiological system involved in the regulation of dietary fat consumption and energy homeostasis; therefore, it is suggested as a possible therapeutic agent for the management of obesity.

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Section: Discussionmentioning

confidence: 99%

A systematic review of the effects of oleoylethanolamide, a high‐affinity endogenous ligand of PPAR‐α, on the management and prevention of obesity

Tutunchi

Saghafi-Asl

Ostadrahimi

2020

Clin Exp Pharma Physio

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“…Mitochondrial disturbances play a crucial role both in aging and in neurodegenerative disorders. Lamichane et al [66] reported that PPAR-α increases genes expression encoding mitochondrial enzymes that are related to lipid metabolism, which include carnitine palmitylotransferase 1 (CPT1), medium-chain acyl-CoA dehydrogenase, acyl-CoA oxidase and fatty acyl-CoA synthase. Additionally, PPAR-α activates genes coding transport proteins of fatty acids (FA) and their derivatives to allow them enter into the β-oxidation pathway.…”

Section: The Role Of Ppars In Regulation Of Mitochondrial Functionmentioning

confidence: 99%

The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer’s Disease and Other Neurodegenerative Disorders

et al. 2020

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Peroxisome proliferator activated receptor alpha (PPAR-α) belongs to the family of ligand-regulated nuclear receptors (PPARs). These receptors after heterodimerization with retinoid X receptor (RXR) bind in promotor of target genes to PPAR response elements (PPREs) and act as a potent transcription factors. PPAR-α and other receptors from this family, such as PPAR-β/δ and PPAR-γ are expressed in the brain and other organs and play a significant role in oxidative stress, energy homeostasis, mitochondrial fatty acids metabolism and inflammation. PPAR-α takes part in regulation of genes coding proteins that are involved in glutamate homeostasis and cholinergic/dopaminergic signaling in the brain. Moreover, PPAR-α regulates expression of genes coding enzymes engaged in amyloid precursor protein (APP) metabolism. It activates gene coding of α secretase, which is responsible for non-amyloidogenic pathway of APP degradation. It also down regulates β secretase (BACE-1), the main enzyme responsible for amyloid beta (Aβ) peptide release in Alzheimer Diseases (AD). In AD brain expression of genes of PPAR-α and PPAR-γ coactivator-1 alpha (PGC-1α) is significantly decreased. PPARs are altered not only in AD but in other neurodegenerative/neurodevelopmental and psychiatric disorder. PPAR-α downregulation may decrease anti-oxidative and anti-inflammatory processes and could be responsible for the alteration of fatty acid transport, lipid metabolism and disturbances of mitochondria function in the brain of AD patients. Specific activators of PPAR-α may be important for improvement of brain cells metabolism and cognitive function in neurodegenerative and neurodevelopmental disorders.

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“…PPARs regulate the transcription of eicosanoid genes and fatty acids (FAs) and are associated with transcriptional activation of peroxisomal FA β-oxidation. Some enzymes involved in carbohydrate and lipid metabolism are directly regulated by PPARs through their interaction with peculiar elements of response in their gene promoters [9]. The anti-inflammatory effect of PPARs is related to lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferatoractivated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

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Pivotal Roles of Peroxisome Proliferator-Activated Receptors (PPARs) and Their Signal Cascade for Cellular and Whole-Body Energy Homeostasis

Cited by 109 publications

References 78 publications

A systematic review of the effects of oleoylethanolamide, a high‐affinity endogenous ligand of PPAR‐α, on the management and prevention of obesity

A systematic review of the effects of oleoylethanolamide, a high‐affinity endogenous ligand of PPAR‐α, on the management and prevention of obesity

The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer’s Disease and Other Neurodegenerative Disorders

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

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