Prolactin-releasing peptide: a new tool for obesity treatment

Obesity is an escalating epidemic, but an effective noninvasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated because peptides have a low stability and limited ability to cross the blood–brain barrier. In this review, we summarize results of several studies with our newly designed lipidized analogs of prolactin-releasing peptide (PrRP). PrRP is involved in feeding and energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF (NPFF)-2 receptor. Acute peripheral administration of myristoylated and palmitoylated PrRP analogs to mice and rats induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight, improved metabolic parameters and attenuated lipogenesis in mice with diet-induced obesity. A strong anorexigenic, body weight-reducing and glucose tolerance-improving effect of palmitoylated-PrRP31 was shown also in diet-induced obese rats after its repeated 2-week-long peripheral administration. Thus, the strong anorexigenic and body weight-reducing effects of palmitoylated PrRP31 and myristoylated PrRP20 make these analogs attractive candidates for antiobesity treatment. Moreover, PrRP receptor might be a new target for obesity therapy.

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Minireview: Finding the Sweet Spot: Peripheral Versus Central Glucagon-Like Peptide 1 Action in Feeding and Glucose Homeostasis

Endocrinology ◽

10.1210/en.2009-0220 ◽

2009 ◽

Vol 150 (7) ◽

pp. 2997-3001 ◽

Cited By ~ 61

Author(s):

Diana L. Williams

Keyword(s):

Body Weight ◽

Insulin Secretion ◽

Food Intake ◽

Glucose Homeostasis ◽

Sweet Spot ◽

Food Intake Regulation ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Intake Regulation ◽

The Brain

Glucagon-like peptide 1 (GLP-1) is both a gut-derived hormone and a neurotransmitter synthesized in the brain. Early reports suggested that GLP-1 acts in the periphery to promote insulin secretion and affect glucose homeostasis, whereas central GLP-1 reduces food intake and body weight. However, current research indicates that in fact, GLP-1 in each location plays a role in these functions. This review summarizes the evidence for involvement of peripheral and brain GLP-1 in food intake regulation and glucose homeostasis and proposes a model for the coordinated actions of GLP-1 at multiple sites.

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The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication

Neuroendocrinology ◽

10.1159/000489263 ◽

2018 ◽

Vol 107 (1) ◽

pp. 91-104 ◽

Cited By ~ 12

Author(s):

Yuko Maejima ◽

Shoko Yokota ◽

Katsuhiko Nishimori ◽

Kenju Shimomura

Keyword(s):

Adipose Tissue ◽

Food Intake ◽

Fat Mass ◽

Physiological Role ◽

Leptin Resistance ◽

Neural Pathways ◽

Feeding Regulation ◽

Food Intake Regulation ◽

Intake Regulation ◽

The Brain

Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk ejection; however, its additional physiological functions were determined 100 years later. Many recent articles have reported newly discovered effects of oxytocin on social communication, bonding, reward-related behavior, adipose tissue, and muscle and food intake regulation. Because oxytocin neurons project to various regions in the brain that contribute to both feeding reward (hedonic feeding) and the regulation of energy balance (homeostatic feeding), the mechanisms of oxytocin on food intake regulation are complicated and largely unknown. Oxytocin neurons in the paraventricular nucleus (PVN) receive neural projections from the arcuate nucleus (ARC), which is an important center for feeding regulation. On the other hand, these neurons in the PVN and supraoptic nucleus project to the ARC. PVN oxytocin neurons also project to the brain stem and the reward-related limbic system. In addition to this, oxytocin induces lipolysis and decreases fat mass. However, these effects in feeding and adipose tissue are known to be dependent on body weight (BW). Oxytocin treatment is more effective in food intake regulation and fat mass decline for individuals with leptin resistance and higher BW, but is known to be less effective in individuals with normal BW. In this review, we present in detail the recent findings on the physiological role of oxytocin in feeding regulation and the anorexigenic neural pathway of oxytocin neurons, as well as the advantage of oxytocin usage for anti-obesity treatment.

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Food Intake Regulation in Body Weight Management

Nutrition Today ◽

10.1097/00017285-200409000-00006 ◽

2004 ◽

Vol 39 (5) ◽

pp. 203-213 ◽

Cited By ~ 10

Author(s):

Kathleen J. Melanson

Keyword(s):

Body Weight ◽

Food Intake ◽

Weight Management ◽

Food Intake Regulation ◽

Intake Regulation

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Faculty Opinions recommendation of Interleukin-7, a new cytokine targeting the mouse hypothalamic arcuate nucleus: role in body weight and food intake regulation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3291956.2978054 ◽

2010 ◽

Author(s):

Y Peng Loh ◽

Joshua J Park

Keyword(s):

Body Weight ◽

Food Intake ◽

Arcuate Nucleus ◽

Interleukin 7 ◽

Hypothalamic Arcuate Nucleus ◽

Food Intake Regulation ◽

Intake Regulation

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Choline and Folic Acid Balance in Diets During Pregnancy Programs Food Intake Regulation in Wistar Rat Offspring (FS08-05-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.fs08-05-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Rola Hammoud ◽

Chih-Sheng Liao ◽

Emanuela Pannia ◽

Mandy Ho ◽

Neil Yang ◽

...

Keyword(s):

Body Weight ◽

Folic Acid ◽

Weight Gain ◽

Food Intake ◽

Body Weight Gain ◽

Control Diet ◽

Wistar Rat ◽

Rat Offspring ◽

Food Intake Regulation ◽

Intake Regulation

Abstract Objectives High gestational folic acid (FA) induces an obesogenic phenotype in male Wistar rat offspring. Imbalances between FA and other methyl-nutrients (i.e., choline) leading to perturbations in the 1-carbon cycle may account for the effects of high FA diets. Canadian women consume high (2–7-fold) intakes of FA, but most are not meeting recommended adequate intakes for choline. Choline is also absent from Canadian prenatal supplements. The objective of this study is to evaluate the effects of the interaction between choline and FA in maternal diets of rats on the 1-carbon cycle, and the programming of food intake, body weight gain and biomarkers of obesity in the offspring later in life. Methods Pregnant Wistar rat dams were fed the AIN-93 G diet with recommended (1X) choline and FA (RCRF, control), or a 5X FA diet with either 0.5X choline (LCHF), 1X choline (RCHF), or 2.5X choline (HCHF). Brain and blood were collected at birth. At weaning one male pup/dam from all groups was maintained on the control diet for 20 weeks then terminated. Dependent measures include weekly body weight-gain and food intake, plasma glucoregulatory hormones and 1-carbon metabolites at birth and post-weaning. Results Increasing choline content to 2.5-fold in a high (5-fold) gestational FA diet (HCHF) led to lower plasma insulin and leptin levels at birth compared to the LCHF and RCHF diets, respectively (P < 0.05). It also led to lower (25%, P = 0.03) plasma 5-methyltetrahydrofolate concentrations at birth compared to the RCHF diet, suggesting more efficient utilization of FA. Offspring born to dams maintained on a high folic acid diet with either low or recommended choline had higher weekly food intake (6%, P < 0.05) and body weight-gain (9%, P < 0.01). In contrast, offspring from dams fed the HCHF gestational diet were not different from those born to dams fed the RCRF (control) diet, highlighting the mitigating effects of a balanced choline and FA gestational diet. Conclusions Increased intakes of choline mitigate the effects of high FA diets. Maternal dietary choline interacts with FA on the long-term programming of food intake regulation in the offspring; emphasizing a need for more attention to improving choline intakes by women of child-bearing age. Funding Sources This research was funded by the Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD).

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Ontogenetic Pattern Changes of Nucleobindin-2/Nesfatin-1 in the Brain and Intestinal Bulb of the Short Lived African Turquoise Killifish

Journal of Clinical Medicine ◽

10.3390/jcm9010103 ◽

2019 ◽

Vol 9 (1) ◽

pp. 103 ◽

Cited By ~ 1

Author(s):

Alessia Montesano ◽

Elena De Felice ◽

Adele Leggieri ◽

Antonio Palladino ◽

Carla Lucini ◽

...

Keyword(s):

Food Intake ◽

Model Organism ◽

Aging Research ◽

Age Related ◽

Nothobranchius Furzeri ◽

Food Intake Regulation ◽

Mammalian Stomach ◽

Regulate Food Intake ◽

Intake Regulation ◽

The Brain

Nesfatin-1 (Nesf-1) was identified as an anorexigenic and well conserved molecule in rodents and fish. While tissue distribution of NUCB2 (Nucleobindin 2)/Nesf-1 is discretely known in vertebrates, reports on ontogenetic expression are scarce. Here, we examine the age-related central and peripheral expression of NUCB2/Nesf-1 in the teleost African turquoise killifish Nothobranchius furzeri, a consolidated model organism for aging research. We focused our analysis on brain areas responsible for the regulation of food intake and the rostral intestinal bulb, which is analogous of the mammalian stomach. We hypothesize that in our model, the stomach equivalent structure is the main source of NUCB2 mRNA, displaying higher expression levels than those observed in the brain, mainly during aging. Remarkably, its expression significantly increased in the rostral intestinal bulb compared to the brain, which is likely due to the typical anorexia of aging. When analyzing the pattern of expression, we confirmed the distribution in diencephalic areas involved in food intake regulation at all age stages. Interestingly, in the rostral bulb, NUCB2 mRNA was localized in the lining epithelium of young and old animals, while Nesf-1 immunoreactive cells were distributed in the submucosae. Taken together, our results represent a useful basis for gaining deeper knowledge regarding the mechanisms that regulate food intake during vertebrate aging.

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The gut–brain axis in vertebrates: implications for food intake regulation

Journal of Experimental Biology ◽

10.1242/jeb.231571 ◽

2021 ◽

Vol 224 (1) ◽

pp. jeb231571

Author(s):

Ayelén Melisa Blanco ◽

Jessica Calo ◽

José Luis Soengas

Keyword(s):

Gastrointestinal Tract ◽

Food Intake ◽

Single Species ◽

Entire Group ◽

Special Focus ◽

Extensive Literature ◽

Energy Status ◽

Food Intake Regulation ◽

Intake Regulation ◽

The Brain

ABSTRACTThe gut and brain are constantly communicating and influencing each other through neural, endocrine and immune signals in an interaction referred to as the gut–brain axis. Within this communication system, the gastrointestinal tract, including the gut microbiota, sends information on energy status to the brain, which, after integrating these and other inputs, transmits feedback to the gastrointestinal tract. This allows the regulation of food intake and other physiological processes occurring in the gastrointestinal tract, including motility, secretion, digestion and absorption. Although extensive literature is available on the mechanisms governing the communication between the gut and the brain in mammals, studies on this axis in other vertebrates are scarce and often limited to a single species, which may not be representative for obtaining conclusions for an entire group. This Review aims to compile the available information on the gut–brain axis in birds, reptiles, amphibians and fish, with a special focus on its involvement in food intake regulation and, to a lesser extent, in digestive processes. Additionally, we will identify gaps of knowledge that need to be filled in order to better understand the functioning and physiological significance of such an axis in non-mammalian vertebrates.

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