Chronic intracerebroventricular infusion of MCH causes obesity in mice

Gomori, Akira; Ishihara, Akane; Ito, Masahiko; Mashiko, Satoshi; Matsushita, Hiroko; Yumoto, Mariko; Ito, Makoto; Tanaka, Takeshi; Tokita, Shigeru; Moriya, M.; Iwaasa, Hisashi; Kanatani, Akio

doi:10.1152/ajpendo.00350.2002

Cited by 200 publications

(125 citation statements)

References 34 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…infusions of either MCH or an MCH-1 receptor antagonist had no effect on daily home-cage activity [12,17,[36][37][38]. It should be noted, however, that in three of these studies, chronic MCH treatment failed to increase food intake [12,36,37]. Clearly, additional studies are required to better understand the impact of acute versus chronic administration of MCH on food intake and locomotor energy expenditure.…”

Section: Discussionmentioning

confidence: 93%

The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle

Santollo

Eckel

2008

Physiology & Behavior

View full text Add to dashboard Cite

Recently, it was shown that that the orexigenic effect of melanin concentrating hormone (MCH) is attenuated by estradiol treatment in ovariectomized (OVX) rats. This suggests that female rats may be less responsive than male rats to the behavioral effects of MCH. To investigate this hypothesis, the effects of lateral ventricular infusions of MCH on food intake, water intake, meal patterns, and running wheel activity were examined in male and female rats. To further characterize the impact of estradiol on MCH-induced food intake, female rats were OVX and tested with and without 17-β-estradiol benzoate (EB) replacement. In support of our hypothesis, food and water intakes following MCH treatment were greater in male rats, relative to female rats. Specifically, the orexigenic effect of MCH was maximal in male rats and minimal in EB-treated OVX rats. In both sexes, the orexigenic effect of MCH was mediated by a selective increase in meal size, which was attenuated in EB-treated OVX rats. MCH induced a short-term (2 h) decrease in wheel running that, unlike its effects on ingestive behavior, was similar in males and females. Thus, estradiol decreases some, but not all, of the behavioral effects of MCH. To examine the influence of endogenous estradiol, food intake was monitored following MCH treatment in ovarian-intact, cycling rats. As predicted by our findings in OVX rats, the orexigenic effect of MCH was attenuated in estrous rats, relative to diestrous rats. We conclude that the female rat's reduced sensitivity to the orexigenic effect of MCH may contribute to sex-and estrous cycle-related differences in food intake.

show abstract

Section: Discussionmentioning

confidence: 93%

The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle

Santollo

Eckel

2008

Physiology & Behavior

View full text Add to dashboard Cite

show abstract

“…It has been shown that the expression level of MCH mRNA increases in leptin-deficient obese (ob/ob) mice as well as in response to fasting in wild-type mice (Qu et al, 1996). It is also been shown that intracerebroventricular administration of MCH causes a rapid increase in food intake (hyperphagia) and obesity (Gomori et al, 2003). Genetic models further confirm the role of MCH in energy homeostasis.…”

Section: Introductionmentioning

confidence: 79%

Late-Onset Leanness in Mice with Targeted Ablation of Melanin Concentrating Hormone Neurons

Alon¹,

Friedman²

2006

J. Neurosci.

107

View full text Add to dashboard Cite

The observation that loss of orexin (hypocretin) neurons causes human narcolepsy raises the possibility that other acquired disorders might also result from loss of hypothalamic neurons. To test this possibility for body weight, mice with selective loss of melanin concentrating hormone (MCH) neurons were generated. MCH was chosen to test because induced mutations of the MCH gene in mice cause hypophagia and leanness. Mice with ablation of MCH neurons were generated using toxin (ataxin-3)-mediated ablation strategy. The mice appeared normal but, after 7 weeks, developed reduced body weight, body length, fat mass, lean mass, and leptin levels. Leanness was characterized by hypophagia and increased energy expenditure. To study the role of MCH neurons on obesity secondary to leptin deficiency, we generated mice deficient in both ob gene product (leptin) and MCH neurons. Absence of MCH neurons in ob/ob mice improved obesity, diabetes, and hepatic steatosis, suggesting that MCH neurons are important mediators of the response to leptin deficiency. These data show that loss of MCH neurons can lead to an acquired leanness. This has implications for the pathogenesis of acquired changes of body weight and might be considered in clinical settings characterized by substantial weight changes later in life.

show abstract

“…Processing of Pmch results in the production of three neuropeptides: neuropeptide glycine-glutamic acid (N-GE), neuropeptide glutamic acid-isoleucine (N-EI), and MCH (41). Pmch mRNA is upregulated after fasting or leptin deficiency (32, 50); third ventricle intracerebroventricular injections of MCH increase food intake and body weight (11,19,22,28,53); Pmch knockout mice are lean due to a decreased food intake and an increased metabolic rate (31, 59); and overexpression of MCH causes obesity (35). In rodents MCH binds to melanin-concentrating hormone receptor 1 (MCH1R), a G protein-coupled receptor expressed throughout the brain (7,33,55,56).…”

mentioning

confidence: 99%

Pmchexpression during early development is critical for normal energy homeostasis

Mul

Berg³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Mul JD, Yi CX, van den Berg SAA, Ruiter M, Toonen PW, van der Elst MCJ, Voshol PJ, Ellenbroek BA, Kalsbeek A, la Fleur SE, Cuppen E. Pmch expression during early development is critical for normal energy homeostasis. Am J Physiol Endocrinol Metab 298: E477-E488, 2010. First published November 24, 2009 doi:10.1152/ajpendo.00154.2009.-Postnatal development and puberty are times of strong physical maturation and require large quantities of energy. The hypothalamic neuropeptide melanin-concentrating hormone (MCH) regulates nutrient intake and energy homeostasis, but the underlying mechanisms are not completely understood. Here we use a novel rat knockout model in which the MCH precursor Pmch has been inactivated to study the effects of loss of MCH on energy regulation in more detail. Pmch Ϫ/Ϫ rats are lean, hypophagic, osteoporotic, and although endocrine parameters were changed in pmch Ϫ/Ϫ rats, endocrine dynamics were normal, indicating an adaptation to new homeostatic levels rather than disturbed metabolic mechanisms. Detailed body weight growth and feeding behavior analysis revealed that Pmch expression is particularly important during early rat development and puberty, i.e., the first 8 postnatal weeks. Loss of Pmch resulted in a 20% lower set point for body weight that was determined solely during this period and remained unchanged during adulthood. Although the final body weight is diet dependent, the Pmch-deficiency effect was similar for all diets tested in this study. Loss of Pmch affected energy expenditure in both young and adult rats, although these effects seem secondary to the observed hypophagia. Our findings show an important role for Pmch in energy homeostasis determination during early development and indicate that the MCH receptor 1 system is a plausible target for childhood obesity treatment, currently a major health issue in first world countries. melanin-concentrating hormone; hypothalamus; childhood obesity; rat knockout model CHILDHOOD OBESITY IS NOW WIDELY recognized as a severe public health issue (43). Treatment with drugs aimed at neural systems involved in the determination of the energy balance could potentially result in a lower energy balance during puberty as well as later in adulthood. Therefore, neuropeptides involved in body weight regulation during early development and puberty are attractive targets for anti-childhood obesity drugs.The neuronal metabolic systems in humans and primates develop prenatally, while in rodents these systems develop during the first 3 postnatal weeks (5, 21). This results in the activation and optimization of neuronal systems during early rodent development. A second important metabolic period is puberty, a period of major growth, hormonal changes, and sexual maturation. In the rat, puberty is characterized by different responses of young-adolescent [postnatal day (PND) 40] and young-adult (PND 60) male rats to environmental cues like stress and cold (17,18). In addition to these age-dependent behavioral differences, the amount of food consumed durin...

show abstract

Chronic intracerebroventricular infusion of MCH causes obesity in mice

Cited by 200 publications

References 34 publications

The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle

The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle

Late-Onset Leanness in Mice with Targeted Ablation of Melanin Concentrating Hormone Neurons

Pmchexpression during early development is critical for normal energy homeostasis

Contact Info

Product

Resources

About