Nitric oxide and l-arginine regulate feeding in satiated rats

Hazut, Noa; Rapps, Kayla; Kristt, Donald A.; Susswein, Abraham J.; Weller, Aron

doi:10.1016/j.appet.2018.09.023

Cited by 7 publications

(2 citation statements)

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“…Even though the AgRP transcription was low, in this obesogenic environment with an abundance of high-fat food available, rats continued to eat and maintain an energy balance surplus. It has been well established that high-fat diet is a rewarding food for rodents, triggering hedonic overfeeding ( 64 , 85 ) and feeding post satiation ( 86 ). Further, obesity leads to aberrant signaling in the ARC ( 29 , 32 , 87 – 90 ) and other hypothalamic structures ( 22 , 26 , 47 , 90 , 91 ), so it was not surprising to quantify low AgRP expression whilst rats continue to over-consume.…”

Section: Discussionmentioning

confidence: 99%

Dieting reverses histone methylation and hypothalamic AgRP regulation in obese rats

et al. 2023

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IntroductionAlthough dieting is a key factor in improving physiological functions associated with obesity, the role by which histone methylation modulates satiety/hunger regulation of the hypothalamus through weight loss remains largely elusive. Canonically, H3K9me2 is a transcriptional repressive post-translational epigenetic modification that is involved in obesity, however, its role in the hypothalamic arcuate nucleus (ARC) has not been thoroughly explored. Here we explore the role that KDM4D, a specific demethylase of residue H3K9, plays in energy balance by directly modulating the expression of AgRP, a key neuropeptide that regulates hunger response.MethodsWe used a rodent model of diet-induced obesity (DIO) to assess whether histone methylation malprogramming impairs energy balance control and how caloric restriction may reverse this phenotype. Using ChIP-qPCR, we assessed the repressive modification of H3K9me2 at the site of AgRP. To elucidate the functional role of KDM4D in reversing obesity via dieting, a pharmacological agent, JIB-04 was used to inhibit the action of KDM4D in vivo.ResultsIn DIO, downregulation of Kdm4d mRNA results in both enrichment of H3K9me2 on the AgRP promoter and transcriptional repression of AgRP. Because epigenetic modifications are dynamic, it is possible for some of these modifications to be reversed when external cues are altered. The reversal phenomenon was observed in calorically restricted rats, in which upregulation of Kdm4d mRNA resulted in demethylation of H3K9 on the AgRP promoter and transcriptional increase of AgRP. In order to verify that KDM4D is necessary to reverse obesity by dieting, we demonstrated that in vivo inhibition of KDM4D activity by pharmacological agent JIB-04 in naïve rats resulted in transcriptional repression of AgRP, decreasing orexigenic signaling, thus inhibiting hunger.DiscussionWe propose that the action of KDM4D through the demethylation of H3K9 is critical in maintaining a stable epigenetic landscape of the AgRP promoter, and may offer a target to develop new treatments for obesity.

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Section: Discussionmentioning

confidence: 99%

Dieting reverses histone methylation and hypothalamic AgRP regulation in obese rats

et al. 2023

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“…During the successive developmental phases, both in B. lanceolatum and B. floridae larvae, Nos expression was observed in the intestine and the club-shaped gland [ 45 , 59 ]. The club-shaped gland is involved in the production of mucus for capturing food particles entering the mouth, and this suggests a role of NO in the feeding behavior that is a conserved feature in other animals [ 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. The neuronal expression of NosC , detected from neurula to larva stages, is a strong indication of the NO’s Involvement in neurogenesis and neurotransmission [ 45 , 49 ].…”

Section: No Function In Cephalochordatesmentioning

confidence: 99%

Nitric Oxide Function and Nitric Oxide Synthase Evolution in Aquatic Chordates

Locascio

Annona

Caccavale

et al. 2023

IJMS

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Nitric oxide (NO) is a key signaling molecule in almost all organisms and is active in a variety of physiological and pathological processes. Our understanding of the peculiarities and functions of this simple gas has increased considerably by extending studies to non-mammal vertebrates and invertebrates. In this review, we report the nitric oxide synthase (Nos) genes so far characterized in chordates and provide an extensive, detailed, and comparative analysis of the function of NO in the aquatic chordates tunicates, cephalochordates, teleost fishes, and amphibians. This comprehensive set of data adds new elements to our understanding of Nos evolution, from the single gene commonly found in invertebrates to the three genes present in vertebrates.

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