Obesity Pharmacotherapy: Current Perspectives and Future Directions

Misra, Monika

doi:10.2174/1573403x11309010006

Cited by 2 publications

(2 citation statements)

References 211 publications

(286 reference statements)

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“…Understanding the cellular and molecular mechanisms mediating information processing in neuronal circuits that regulate energy homeostasis is essential to devise specific pharmacological strategies, which assist obese patients in starting and maintaining a program of weight loss with no or minimized side effects on other neuronal systems (Gouni-Berthold et al, 2013; Holes-Lewis et al, 2013; Misra, 2013). Important microcircuits in control of energy balance are localized in the arcuate nucleus of the hypothalamus (ARH), which contains two main neuron populations with antagonistic functions: Neuropeptide Y and agouti-related peptide (NPY/AgRP) co-expressing neurons signaling hunger, promoting food intake, and pro-opiomelanocortin (POMC) - expressing neurons which signal satiety (Sohn et al, 2013; Varela and Horvath, 2012).…”

Section: Introductionmentioning

confidence: 99%

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin

Paeger

Karakasilioti

Altmüller

et al. 2017

eLife

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In the arcuate nucleus of the hypothalamus (ARH) satiety signaling (anorexigenic) pro-opiomelanocortin (POMC)-expressing and hunger signaling (orexigenic) agouti-related peptide (AgRP)-expressing neurons are key components of the neuronal circuits that control food intake and energy homeostasis. Here, we assessed whether the catecholamine noradrenalin directly modulates the activity of these neurons in mice. Perforated patch clamp recordings showed that noradrenalin changes the activity of these functionally antagonistic neurons in opposite ways, increasing the activity of the orexigenic NPY/AgRP neurons and decreasing the activity of the anorexigenic POMC neurons. Cell type-specific transcriptomics and pharmacological experiments revealed that the opposing effect on these neurons is mediated by the activation of excitatory α1A - and β- adrenergic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via α2A – adrenergic receptors. Thus, the coordinated differential modulation of the key hypothalamic neurons in control of energy homeostasis assigns noradrenalin an important role to promote feeding.DOI: http://dx.doi.org/10.7554/eLife.25770.001

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Section: Introductionmentioning

confidence: 99%

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin

Paeger

Karakasilioti

Altmüller

et al. 2017

eLife

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“…(3), non-alcoholic fatty liver disease (NAFLD) (3) and renal damage (5). However, few therapeutic strategies are available for the longterm treatment of obesity, with some of them largely ineffective (6). It is urgently needed to find new directions for the effective treatment strategies.…”

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confidence: 99%

Role of purinergic signalling in obesity-associated end-organ damage: focus on the effects of natural plant extracts

et al. 2023

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Obesity has become one of the major public health problems in both the developing and developed countries. Recent studies have suggested that the purinergic signalling is involved in obesity-associated end-organ damage through purine P1 and P2 receptors. In the search for new components for the treatments of obesity, we and other researchers have found much evidence that natural plant extracts may be promising novel therapeutic approaches by modulating purinergic signalling. In this review, we summarize a critical role of purinergic signalling in modulating obesity-associated end-organ damage, such as overhigh appetite, myocardial ischemia, inflammation, atherosclerosis, non-alcoholic fatty liver disease (NAFLD), hepatic steatosis and renal inflammation. Moreover, we focus on the potential roles of several natural plant extracts, including quercetin, resveratrol/trans-resveratrol, caffeine, evodiamine and puerarin, in alleviating obesity-associated end-organ damage via purinergic signalling. We hope that the current knowledge of the potential roles of natural plant extracts in regulating purinergic signalling would provide new ideas for the treatment of obesity and obesity-associated end-organ damage.

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Obesity Pharmacotherapy: Current Perspectives and Future Directions

Cited by 2 publications

References 211 publications

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin

Role of purinergic signalling in obesity-associated end-organ damage: focus on the effects of natural plant extracts

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