Neurotrophic factor control of satiety and body weight

Xu, Baoji; Xie, Xiangyang

doi:10.1038/nrn.2016.24

Cited by 185 publications

(154 citation statements)

References 162 publications

(214 reference statements)

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…It has been established that estradiol suppresses appetite through hypothalamic ERα and that this activity is interactively mediated by hypothalamic SF-1 and oxytocin [18][19][20][21][22][23][24][25]. In addition, hypothalamic aromatase (CYP19a1) plays pivotal roles in the appropriate regulation of body weight in rodents [6].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, hypothalamic aromatase (CYP19a1) plays pivotal roles in the appropriate regulation of body weight in rodents [6]. Furthermore, hypothalamic nesfatin-1 (NUCB2), PACAP, and BDNF mediate the anorectic activity of leptin in the hypothalamus [22][23][24][25]. However, because we could not examine the effects of prolonged high-fat diet consumption on the levels of these factors in the present study it remains unclear whether the changes in the expression levels of these factors that occur in response to the consumption of a high-fat diet are altered in IUGR rats in adulthood.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The effects of prenatal undernutrition and a high-fat postnatal diet on central and peripheral orexigenic and anorexigenic factors in female rats

et al. 2017

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effects of prenatal undernutrition and a high-fat postnatal diet on central and peripheral orexigenic and anorexigenic factors in female rats

et al. 2017

View full text Add to dashboard Cite

“…Recently, a de novo mutations in TrkB was found in a boy with severe obesity and impairment in learning, memory and nociception, and in a girl with hyperphagia and severe obesity [66].…”

Section: Other Types Of Non-syndromic Genetic Obesitymentioning

confidence: 99%

New Thoughts on Pediatric Genetic Obesity: Pathogenesis, Clinical Characteristics and Treatment Approach

Stagi¹,

Bianconi²,

Sammarco³

et al. 2017

Adiposity - Omics and Molecular Understanding

View full text Add to dashboard Cite

Historically, some genetic syndromes and monogenic forms of obesity have been identified by clinical features and by sequencing candidate genes in patients with severe obesity. The phenotypic expression of genetic factors involved in obesity is variable, thereby allowing to distinguish several clinical pictures of obesity. Monogenic obesity is described as rare and severe early-onset obesity with abnormal feeding behavior and endocrine disorders. Many of the findings emerged from studying families who displayed a classical Mendelian pattern of inheritance. On the contrary, patients with syndromic obesity show a various degree of intellectual disability, different dysmorphic features, and organ-specific abnormalities. But to date, not all involved genes have been identified so far. New diagnostic tools, such as genome-wide studies, array CGH, and whole-exome sequencing, have highlighted more complex models of inheritance, and even more candidate genes were identified. This increase of knowledge may provide insights into the mechanisms involved in the regulation of body weight and finally lead to specific treatments. In these patients, hyperphagia is often a primary phenotypic component. Substantial gaps in understanding the molecular basis of inherited hyperphagia syndromes are present today with a lack of mechanistic targets that can serve as a basis for pharmacologic and behavioral treatments. We have evaluated retrospectively the literature data on weight, body mass index (BMI), clinical features, treatments, and treatment response in pediatric patients with forms of genetic obesity. However, this chapter provides an updated picture of emerging knowledge outlined by the more comprehensive genetic approaches, trying to outline more candidate genes for these forms of genetic obesity. Relevant papers will be identified through systematic searches of the PubMed, EMBASE and Cochrane databases. All published studies in the English language concerning these disorders will be evaluated. Keywords in the

show abstract

“…This specialized region of the brain is responsible for integrating neural and endocrine signaling to maintain homeostasis, utilizing discreet nuclei to regulate processes such as appetite, sleep, aggression, and body temperature (Jego et al, 2013;Falkner et al, 2016;Fischer et al, 2016;Xu and Xie, 2016). Moreover, GUCY2C is enriched in the arcuate nucleus, a collection of neurons positioned ventrolateral to the third ventricle of the brain, which serves as the central site for energy balance by regulating appetite to ensure that food intake matches energy expenditure Xu and Xie, 2016). This periventricular organ receives its blood supply through fenestrated capillaries, allowing it unique access to endocrine hormone signals from distant sites outside the nervous system (Zhang et al, 2015).…”

Section: The Gucy2c Endocrine Hormone Axis In Appetite and Satietymentioning

confidence: 99%

Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer

Blomain

Merlino

Pattison

et al. 2016

Molecular Pharmacology

View full text Add to dashboard Cite

Obesity has emerged as a principal cause of mortality worldwide, reflecting comorbidities including cancer risk, particularly in colorectum. Although this relationship is established epidemiologically, molecular mechanisms linking colorectal cancer and obesity continue to be refined. Guanylyl cyclase C (GUCY2C), a membrane-bound guanylyl cyclase expressed in intestinal epithelial cells, binds the paracrine hormones guanylin and uroguanylin, inducing cGMP signaling in colorectum and small intestine, respectively. Guanylin is the most commonly lost gene product in sporadic colorectal cancer, and its universal loss early in transformation silences GUCY2C, a tumor suppressor, disrupting epithelial homeostasis underlying tumorigenesis. In small intestine, eating induces endocrine secretion of uroguanylin, the afferent limb of a novel gut-brain axis that activates hypothalamic GUCY2C-cGMP signaling mediating satiety opposing obesity. Recent studies revealed that dietinduced obesity suppressed guanylin and uroguanylin expression in mice and humans. Hormone loss reflects reversible calorieinduced endoplasmic reticulum stress and the associated unfolded protein response, rather than the endocrine, adipokine, or inflammatory milieu of obesity. Loss of intestinal uroguanylin secretion silences the hypothalamic GUCY2C endocrine axis, creating a feed-forward loop contributing to hyperphagia in obesity. Importantly, calorie-induced guanylin loss silences the GUCY2C-cGMP paracrine axis underlying obesity-induced epithelial dysfunction and colorectal tumorigenesis. Indeed, genetically enforced guanylin replacement eliminated diet-induced intestinal tumorigenesis in mice. Taken together, these observations suggest that GUCY2C hormone axes are at the intersection of obesity and colorectal cancer. Moreover, they suggest that hormone replacement that restores GUCY2C signaling may be a novel therapeutic paradigm to prevent both hyperphagia and intestinal tumorigenesis in obesity.

show abstract

Neurotrophic factor control of satiety and body weight

Cited by 185 publications

References 162 publications

The effects of prenatal undernutrition and a high-fat postnatal diet on central and peripheral orexigenic and anorexigenic factors in female rats

The effects of prenatal undernutrition and a high-fat postnatal diet on central and peripheral orexigenic and anorexigenic factors in female rats

New Thoughts on Pediatric Genetic Obesity: Pathogenesis, Clinical Characteristics and Treatment Approach

Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer

Contact Info

Product

Resources

About