PPARs and Mitochondrial Metabolism: From NAFLD to HCC

Mello, Tommaso; Materozzi, Maria; Galli, Andrea

doi:10.1155/2016/7403230

Cited by 68 publications

(57 citation statements)

References 211 publications

(240 reference statements)

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“…Numerous studies demonstrate that MS predisposing to different chronic disease characteristics of western countries like non-insulin dependent diabetes (NIDS) [6], psoriasis [7], obesity [8], cardiovascular diseases (CVD) [9, 10], osteoarthritis [11], neurodegenerative diseases like Alzheimer syndrome [12], the most common hormone-dependent tumours like breast [13] and prostate [14], as well as pancreas [15], colorectal cancer [16] and hepatocellular carcinoma [17]…”

Section: Introductionmentioning

confidence: 99%

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

et al. 2017

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This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

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Section: Introductionmentioning

confidence: 99%

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

et al. 2017

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“…PPAR α and PPAR γ play critical roles in regulation of peroxisomal and mitochondrial biogenesis . Our laboratory and others have reported that statin treatment induces the expression and activities of PPARs through the attenuation of RhoA/ROCK activity .…”

Section: Resultsmentioning

confidence: 89%

“…PPARa and PPARc play critical roles in regulation of peroxisomal and mitochondrial biogenesis. 57,58 Our laboratory and others have reported that statin treatment induces the expression and activities of PPARs 35,59,60 through the attenuation of RhoA/ROCK activity. 35,54 Therefore, we next investigated the effects of LOVA and AICAR and their combination on the expression of PPARa and PPARc.…”

Section: Lova and Aicar Treatments Cooperatively Enhance The Expressimentioning

confidence: 98%

Combination therapy of lovastatin and AMP‐activated protein kinase activator improves mitochondrial and peroxisomal functions and clinical disease in experimental autoimmune encephalomyelitis model

et al. 2018

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Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of a combination of lovastatin and AMP-activated protein kinase (AMPK) activator (AICAR) on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes and myelin/axons, and therefore partial attenuation of clinical disease in EAE mice. However, treatment of EAE mice with the lovastatin and AICAR combination provided greater protection of mitochondria/peroxisomes and myelin/axons, and greater improvement in clinical disease compared with individual drug treatments. In spinal cords of EAE mice, lovastatin-mediated inhibition of RhoA and AICAR-mediated activation of AMPK cooperatively enhanced the expression of the transcription factors and regulators (e.g. PPARα/β, SIRT-1, NRF-1, and TFAM) required for biogenesis and the functions of mitochondria (e.g. OXPHOS, MnSOD) and peroxisomes (e.g. PMP70 and catalase). In summary, these studies document that oral medication with a combination of lovastatin and AICAR, which are individually known to have immunomodulatory effects, provides potent protection and repair of inflammation-induced loss and dysfunction of mitochondria and peroxisomes as well as myelin and axonal abnormalities in EAE. As statins are known to provide protection in progressive MS (Phase II study), these studies support that supplementation statin treatment with an AMPK activator may provide greater efficacy against MS.

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“…There are three members in humans and four in each of the fish species investigated (Table 1). PPARs are crucial in the regulation of lipids (27,57). The pufferfish (Takifugu and Tetraodon) genomes both show two PPARα NRs similar to F. heteroclitus , while the Atlantic salmon ( Salmo salar ) and zebrafish ( D. rerio ) genomes have two members of the PPARβ/δ group (41,58,59).…”

Section: Resultsmentioning

confidence: 99%

Annotation of the Nuclear Receptors in an Estuarine Fish species, Fundulus heteroclitus

Baldwin

Boswell

Ginjupalli

et al. 2017

Nuclear Receptor Research

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The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness. F. heteroclitus have at least 74 NRs spanning all seven gene subfamilies. F. heteroclitus is unique in that no RXRα member was found within the genome. Interestingly, some of the NRs are highly conserved between species, while others show a higher degree of divergence such as PXR, SF1, and ARα. Fundulus like other fish species show expansion of the RAR (NR1B), Rev-erb (NR1D), ROR (NR1F), COUPTF (NR2F), ERR (NR3B), RXR (NR2B), and to a lesser extent the NGF (NR4A), and NR3C steroid receptors (GR/AR). Of particular interest is the co-expansion of opposing NRs, Reverb-ROR, and RAR/RXR-COUPTF.

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PPARs and Mitochondrial Metabolism: From NAFLD to HCC

Cited by 68 publications

References 211 publications

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

Combination therapy of lovastatin and AMP‐activated protein kinase activator improves mitochondrial and peroxisomal functions and clinical disease in experimental autoimmune encephalomyelitis model

Annotation of the Nuclear Receptors in an Estuarine Fish species, Fundulus heteroclitus

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