Proof of concept study: does fenofibrate have a role in sleep apnoea syndrome?

Bruckert, Éric; Duchêne, Emilie; Bonnefont‐Rousselot, Dominique; Hansel, Boris; Ansquer, Jean-Claude; Dubois, Andre; Gaymard, Bertrand

doi:10.1185/03007991003693581

Cited by 9 publications

(3 citation statements)

References 33 publications

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“…In a proof-of-concept clinical study, fenofibrate showed positive effects in obstructive sleep apnea by decreasing the frequency of oxygen desaturation, apnea, and non-cortical micro-awakenings per hours [324]. Such benefits were not observed with pioglitazone in obstructive sleep apnea, emphasizing the distinct role of each PPAR members [325].…”

Section: Miscellaneous Health Conditionsmentioning

confidence: 96%

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Cheng

Tan

Low

et al. 2019

IJMS

177

152

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Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that govern the expression of genes responsible for energy metabolism, cellular development, and differentiation. Their crucial biological roles dictate the significance of PPAR-targeting synthetic ligands in medical research and drug discovery. Clinical implications of PPAR agonists span across a wide range of health conditions, including metabolic diseases, chronic inflammatory diseases, infections, autoimmune diseases, neurological and psychiatric disorders, and malignancies. In this review we aim to consolidate existing clinical evidence of PPAR modulators, highlighting their clinical prospects and challenges. Findings from clinical trials revealed that different agonists of the same PPAR subtype could present different safety profiles and clinical outcomes in a disease-dependent manner. Pemafibrate, due to its high selectivity, is likely to replace other PPARα agonists for dyslipidemia and cardiovascular diseases. PPARγ agonist pioglitazone showed tremendous promises in many non-metabolic disorders like chronic kidney disease, depression, inflammation, and autoimmune diseases. The clinical niche of PPARβ/δ agonists is less well-explored. Interestingly, dual- or pan-PPAR agonists, namely chiglitazar, saroglitazar, elafibranor, and lanifibranor, are gaining momentum with their optimistic outcomes in many diseases including type 2 diabetes, dyslipidemia, non-alcoholic fatty liver disease, and primary biliary cholangitis. Notably, the preclinical and clinical development for PPAR antagonists remains unacceptably deficient. We anticipate the future design of better PPAR modulators with minimal off-target effects, high selectivity, superior bioavailability, and pharmacokinetics. This will open new possibilities for PPAR ligands in medicine.

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Section: Miscellaneous Health Conditionsmentioning

confidence: 96%

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Cheng

Tan

Low

et al. 2019

IJMS

177

152

View full text Add to dashboard Cite

show abstract

“… 68 Clinical studies have also shown that fenofibrate can be used to improve the clinical symptoms of OSA by reducing blood lipid. 69 Fenofibrate also reduces inflammation in the retina and vascular endothelium, 70 , 71 whereas the activation of Ppar α alleviates NF-κB phosphorylation. 72 Because of the complexity of the mechanism of fenofibrate on lipid metabolism, we believe its functional machinery on lacrimal gland deserves further research.…”

Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnea Affects Lacrimal Gland Function

Wang

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine the effect of obstructive sleep apnea syndrome (OSA) on lacrimal gland function and its mechanism. Methods Male mice aged seven to eight weeks were housed in cages with cyclic intermittent hypoxia to mimic OSA, and the control group was kept in a normal environment. Slit-lamp observation, fluorescein staining, and corneal sensitivity detection are used to assess cornea changes. Tear secretion was detected by phenol red cotton thread, and the pathological changes of lacrimal gland were observed by hematoxylin and eosin staining, oil red O staining, cholesterol and triglyceride kits, immunofluorescence staining, immunohistochemical staining, real-time polymerase chain reaction, transmission electron microscopy, and Western blot. Results Studies revealed a decreased tear secretion, corneal epithelial defects and corneal hypersensitivity. Myoepithelial cell damage, abnormal lipid accumulation, reduced cell proliferation, increased apoptosis and inflammatory cell infiltration in the lacrimal gland were also seen. Hif α and NF-κB signaling pathways, moreover, were activated, while Pparα was downregulated, in the lacrimal glands of OSA mice. Fenofibrate treatment significantly alleviated pathological changes of the lacrimal gland induced by OSA. Conclusion OSA disturbs the Hifα / Pparα /NF-κB signaling axis, which affects lacrimal gland structure and function and induces dry eye.

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“…Prospective studies are warranted to determine whether poor sleep affects energy homeostasis, if energy homeostasis affects poor sleep, or both. For example, fenofibrate, a PPARα agonist used to improve triglycerides and cholesterol, showed preliminary efficacy for obstructive sleep apnea [90]. Given the demonstration that inclusion of fenofibrate with antiretroviral therapy to treat dyslipidemia in HIV-infected persons was superior to statin therapy [91], further studies to evaluate for concomittent impact on sleep are warranted.…”

Section: Discussionmentioning

confidence: 99%

Sleep disruption and duration are associated with variants in genes involved in energy homeostasis in adults with HIV/AIDS

et al. 2021

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Objective: To determine whether selected genes and plasma markers involved in energy homeostasis are associated with sleep disruption or duration in adults with HIV/AIDS. Methods: A sample of 289 adults with HIV/AIDS wore a wrist actigraph for 72 hours to estimate total sleep time (TST) and wake after sleep onset (WASO). Twenty-three single nucleotide polymorphisms (SNP) spanning 5 energy homeostasis genes (adiponectin [ADIPOQ], ghrelin [GHRL], leptin [LEP], peroxisome proliferator-activated receptor-alpha [PPARA], and -gamma [PPARG]) were genotyped using a custom array. Plasma markers of energy homeostasis (adiponectin, ghrelin, leptin) were measured by commercial multiplex assay.Results: After adjusting for demographic and clinical characteristics (race/ethnicity, gender, CD4 cell count, waist circumference, medications), both WASO and TST were associated with SNPs in ADIPOQ (rs182052), LEP (rs10244329, rs3828942), PPARA (rs135551, rs4253655), and PPARG (rs709151). Additional SNPs in ADIPOQ were associated with WASO (rs1501299, rs3821799, rs6773957) and TST (rs2241766). TST was also associated with SNPs in GHRL (rs26802), LEP (rs11760956), PPARA (rs135547, rs8138102, rs4253776), and PPARG (rs12490265, rs796313).Many covariate-adjusted associations involved a significant interaction with markers of HIV (viral load, years since diagnosis). Among plasma markers, higher adiponectin was associated with less WASO, higher ghrelin and glucose levels with shorter TST, and higher leptin with longer TST.Conclusions: Replication of SNPs in all five genes and three plasma markers of energy homeostasis were associated with objective sleep measures. HIV disease influenced many of the associations. Findings strengthen evidence for associations between energy homeostasis genetics and poor sleep, and provide direction for pharmacological intervention research.

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Proof of concept study: does fenofibrate have a role in sleep apnoea syndrome?

Abstract: The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome.

Cited by 9 publications

References 33 publications

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Obstructive Sleep Apnea Affects Lacrimal Gland Function

Sleep disruption and duration are associated with variants in genes involved in energy homeostasis in adults with HIV/AIDS

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