A critical update on the l<scp>eptin‐melanocortin</scp> system

Lavoie, O; Michael, Natalie J.; Caron, Alexandre

doi:10.1111/jnc.15765

Cited by 17 publications

(18 citation statements)

References 235 publications

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“…By contrast, in the 'starved state', low leptin levels activate AgRP/NPY neurons and inhibit POMC neurons, promoting food intake. 66 Thus, the leptin-melanocortin pathway illustrates how leptin, a hormone reflective of fat mass, regulates feeding behaviour.…”

Section: The Leptin-melanocortin Pathway and Appetite Controlmentioning

confidence: 99%

“…In the fed state, as well, leptin binds to AgRP/NPY‐releasing neurons in the arcuate nucleus of the hypothalamus, to inhibit the release of AgRP/NPY, whose actions are generally opposite to that of α‐MSH. By contrast, in the ‘starved state’, low leptin levels activate AgRP/NPY neurons and inhibit POMC neurons, promoting food intake 66 . Thus, the leptin–melanocortin pathway illustrates how leptin, a hormone reflective of fat mass, regulates feeding behaviour.…”

Section: Genetics Factors Associated With Obesitymentioning

confidence: 99%

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The melanocortin‐4 receptor pathway and the emergence of precision medicine in obesity management

Fansa,

Acosta

2024

Diabetes Obesity Metabolism

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Over the past few decades, there has been a global surge in the prevalence of obesity, rendering it a globally recognized epidemic. Contrary to simply being a medical condition, obesity is an intricate disease with a multifactorial aetiology. Understanding the precise cause of obesity remains a challenge; nevertheless, there seems to be a complex interplay among biological, psychosocial and behavioural factors. Studies on the genetic factors of obesity have revealed several pathways in the brain that play a crucial role in food intake regulation. The best characterized pathway, thus far, is the leptin–melanocortin pathway, from which disruptions are responsible for the majority of monogenic obesity disorders. The effectiveness of conservative lifestyle interventions in addressing monogenic obesity has been limited. Therefore, it is crucial to complement the management strategy with pharmacological and surgical options. Emphasis has been placed on developing drugs aimed at replacing the absent signals, with the goal of restoring the pathway. In both monogenic and polygenic forms of obesity, outcomes differ across various interventions, likely due to the multifaceted nature of the disease. This underscores the need to explore alternative therapeutic strategies that can mitigate this heterogeneity. Precision medicine can be regarded as a powerful tool that can address this concern, as it values the understanding of the underlying abnormality triggering the disease and provides a tailored treatment accordingly. This would assist in optimizing outcomes of the current therapeutic approaches and even aid in the development of novel treatments capable of more effectively managing the global obesity epidemic.

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Section: The Leptin-melanocortin Pathway and Appetite Controlmentioning

confidence: 99%

Section: Genetics Factors Associated With Obesitymentioning

confidence: 99%

The melanocortin‐4 receptor pathway and the emergence of precision medicine in obesity management

Fansa,

Acosta

2024

Diabetes Obesity Metabolism

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“…The other is responsible for expressing anorexigenic pro-opiomelanocortin (POMC), which gives rise to ɑ-melanocyte stimulating hormone (ɑ-MSH) ( Zhan et al, 2013 ). The interplay between AgRP/NPY and POMC neurons is affected by circulating hormones (leptin, ghrelin, insulin), leading to the regulation of energy and glucose homeostasis ( Lavoie et al, 2023 ). AgRP and ɑ-MSH play opposite roles via the stimulation or inhibition of the melanocortin 3 and 4 receptors in the paraventricular nucleus, whereas NPY acts on Y1/Y5 receptors ( Valassi et al, 2008 ; Waterson et al, 2015 ; Nuzzaci et al, 2015 ).…”

Section: Programming Effects Of Preterm Birth On the Energy Control S...mentioning

confidence: 99%

“…In addition, GABAergic neurons mediate the anorexigenic effects of leptin on POMC neurons ( Fig. 1 ) ( Lavoie et al, 2023 ). Aside from the regulatory role in food intake, AgRP/NPY and POMC neurons are also involved in glucose production and metabolism ( Engström Ruud et al, 2020 ; Steculorum et al, 2016 ; Xu et al, 2018 ).…”

Section: Programming Effects Of Preterm Birth On the Energy Control S...mentioning

confidence: 99%

Preterm birth: A neuroinflammatory origin for metabolic diseases?

Diao,

Chen,

Benani

et al. 2024

Brain, Behavior, & Immunity - Health

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“…Leptin is a peripheral hormone, released mostly from white adipose tissue (WAT), whose blood levels are proportional to the amount of body fat stored [4]. The main site of action of leptin in the brain is the hypothalamus [5], where it decreases food intake and increases energy expenditure [6]. Interestingly, the centrally mediated effect of leptin on energy expenditure depends on the activation of the sympathetic nervous system (SNS) that innervates WAT and brown adipose tissue (BAT), among many organs.…”

Section: Introductionmentioning

confidence: 99%

Multi-Organ Increase in Norepinephrine Levels after Central Leptin Administration and Diet-Induced Obesity

Fernandois,

Vázquez,

Barroso

et al. 2023

IJMS

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Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.

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A critical update on the leptin‐melanocortin system

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 17 publications

References 235 publications

The melanocortin‐4 receptor pathway and the emergence of precision medicine in obesity management

The melanocortin‐4 receptor pathway and the emergence of precision medicine in obesity management

Preterm birth: A neuroinflammatory origin for metabolic diseases?

Multi-Organ Increase in Norepinephrine Levels after Central Leptin Administration and Diet-Induced Obesity

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