Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats

1999 ◽  
Vol 96 (3) ◽  
pp. 307-312 ◽  
Author(s):  
Simon DRYDEN ◽  
Peter KING ◽  
Lucy PICKAVANCE ◽  
Patrick DOYLE ◽  
Gareth WILLIAMS
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Leptin Receptor ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Zucker Rat ◽  
Direct Effects ◽  
The Central Nervous System

Leptin inhibits feeding and decreases body weight. It may act partly by inhibiting hypothalamic neurons that express neuropeptide Y, a powerful inducer of feeding and obesity. These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. We compared the effects of three doses of leptin given intracerebroventricularly and three doses of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. In lean rats, 4-h food intake was reduced in a dose-related fashion (P< 0.01) by all intracerebroventricular leptin doses and by intraperitoneal doses of 300 and 600 μg/kg. Neuropeptide Y mRNA levels were reduced by 28% and 21% after the highest intracerebroventricular and intraperitoneal doses respectively (P< 0.01 for both). In fatty rats, only the highest intracerebroventricular leptin dose reduced food intake (by 22%; P< 0.01). Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P< 0.01) after the highest intracerebroventricular leptin dose. Intraperitoneal injection had no effect on food intake and neuropeptide Y mRNA. The fa/fa Zucker rat is therefore less sensitive to leptin given intracerebroventricularly and particularly intraperitoneally, suggesting that the fa mutation interferes both with leptin's direct effects on neurons and its transport into the central nervous system. Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons.

The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

2019 ◽  
Vol 20 (7) ◽  
pp. 750-758 ◽  
Author(s):  
Yi Wu ◽  
Hengxun He ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropeptide Y ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
Vital Role ◽  
Gut Peptides ◽  
Nonalcoholic Fatty Liver ◽  
The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

Gastrointestinal Satiety Signals I. An overview of gastrointestinal signals that influence food intake

2004 ◽  
Vol 286 (1) ◽  
pp. G7-G13 ◽  
Author(s):  
Stephen C. Woods
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Food Intake ◽  
Social Situation ◽  
Meal Size ◽  
Gi Tract ◽  
The Social ◽  
Adiposity Signals ◽  
The Central Nervous System

An overview is presented of those signals generated by the gastrointestinal (GI) tract during meals that interact with the central nervous system to create a sensation of fullness and satiety. Although dozens of enzymes, hormones, and other factors are secreted by the GI tract in response to food in the lumen, only a handful are able to influence food intake directly. Most of these cause meals to terminate and hence are called satiety signals, with CCK being the most investigated. Only one GI signal, ghrelin, that increases meal size has been identified. The administration of exogenous CCK or other satiety signals causes smaller meals to be consumed, whereas blocking the action of endogenous CCK or other satiety signals causes larger meals to be consumed. Satiety signals are relayed to the hindbrain, either indirectly via nerves such as the vagus from the GI tract or else directly via the blood. Most factors that influence how much food is eaten during individual meals act by changing the sensitivity to satiety signals. This includes adiposity signals as well as habits and learning, the social situation, and stressors.

Interleukin-8 modulates feeding by direct action in the central nervous system

1993 ◽  
Vol 265 (4) ◽  
pp. R877-R882 ◽  
Author(s):  
C. R. Plata-Salaman ◽  
J. P. Borkoski
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Food Intake ◽  
Direct Action ◽  
Intraperitoneal Administration ◽  
Interleukin 8 ◽  
Short Term ◽  
Lipopolysaccharide Endotoxin ◽  
The Central Nervous System ◽  
Necrosis Factor

Interleukin-8 (IL-8) is released in response to infection, inflammation, and trauma. The most important stimuli for IL-8 release during these pathological processes are IL-1, tumor necrosis factor, and bacterial lipopolysaccharide (endotoxin), factors that have been shown to suppress feeding. In the present study, the participation of IL-8 on the central regulation of feeding was investigated. Intracerebroventricular (icv) microinfusion of recombinant human IL-8 (rhIL-8, 1.0-100 ng/rat) suppressed the short-term (2-h) food intake. The most effective dose of rhIL-8, 20 ng, decreased 2-h food intake by 25% and nighttime food intake by 23%. Intracerebroventricular microinfusion of anti-rhIL-8 antibody (200 and 500 ng) blocked the effect of 20 ng rhIL-8 on 2-h and nighttime food intakes. Computerized analysis of behavioral patterns for the 2-h period demonstrated a specific reduction of meal size (by 33%), whereas meal frequency and meal duration were not affected after the icv microinfusion of 20 ng rhIL-8. This short-term food intake suppression by icv rhIL-8 was accompanied by a small, but significant, increase in cerebrospinal fluid-brain and rectal temperatures. Intraperitoneal administration of rhIL-8 in doses equivalent to those administered centrally had no effect on food intake. The results suggest that IL-8 acts directly in the central nervous system to decrease feeding. This effect of IL-8 may contribute to the food intake suppression frequently accompanying pathological processes.

scholarly journals Leptin Receptor Signaling and Action in the Central Nervous System

Obesity ◽  
2006 ◽  
Vol 14 ◽  
pp. 208S-212S ◽  
Author(s):  
Rebecca L. Leshan ◽  
Marie Björnholm ◽  
Heike Münzberg ◽  
Martin G. Myers
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Leptin Receptor ◽  
Receptor Signaling ◽  
The Central Nervous System

Insulin: its relationship to the central nervous system and to the control of food intake and body weight

1985 ◽  
Vol 42 (5) ◽  
pp. 1063-1071 ◽  
Author(s):  
S C Woods ◽  
D Porte ◽  
E Bobbioni ◽  
E Ionescu ◽  
J F Sauter ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
The Central Nervous System

scholarly journals Leptin Sensitivity in the Developing Rat Hypothalamus

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 6073-6082 ◽  
Author(s):  
A.-S. Carlo ◽  
M. Pyrski ◽  
C. Loudes ◽  
A. Faivre-Baumann ◽  
J. Epelbaum ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Leptin Receptor ◽  
Primary Cultures ◽  
Cytokine Signaling ◽  
Neuronal Cultures ◽  
Mrna Levels ◽  
Leptin Signaling ◽  
Leptin Sensitivity

In adults, the adipocyte-derived hormone, leptin, regulates food intake and body weight principally via the hypothalamic arcuate nucleus (ARC). During early postnatal development, leptin functions to promote the outgrowth of neuronal projections from the ARC, whereas a selective insensitivity to the effects of leptin on food intake appears to exist. To investigate the mechanisms underlying the inability of leptin to regulate food intake during early development, leptin signaling was analyzed both in vitro using primary cultures of rat embryonic ARC neurones and in vivo by challenging early postnatal rats with leptin. In neuronal cultures, despite the presence of key components of the leptin signaling pathway, no detectable activation of either signal transducer and activator of transcription 3 or the MAPK pathways by leptin was detected. However, leptin down-regulated mRNA levels of proopiomelanocortin and neuropeptide Y and decreased somatostatin secretion. Leptin challenge in vivo at postnatal d (P) 7, P14, P21, and P28 revealed that, in contrast to adult and P28 rats, mRNA levels of neuropeptide Y, proopiomelanocortin, agouti-related peptide and cocaine- and amphetamine-regulated transcript were largely unaffected at P7, P14, and P21. Furthermore, leptin stimulation increased the suppressor of cytokine signaling-3 mRNA levels at P14, P21, and P28 in several hypothalamic nuclei but not at P7, indicating that selective leptin insensitivity in the hypothalamus is coupled to developmental shifts in leptin receptor signaling. Thus, the present study defines the onset of leptin sensitivity in the regulation of energy homeostasis in the developing hypothalamus.

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