Leptin-like effects of MTII are augmented in MSG-obese rats

Kim, Yong-Woon; Choi, Dong-Weon; Park, Yong-Hoon; Huh, Jung-Yoon; Won, Kyu Chang; Choi, Kyung‐Sik; Park, Soyoung; Kim, Jong-Yeon; Lee, Suck-Kang

doi:10.1016/j.regpep.2004.10.006

Cited by 25 publications

(9 citation statements)

References 27 publications

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“…The hypothalamus was then harvested, stored in liquid nitrogen, and analyzed using the method employed by Kim et al [15]. Briefly, the hypothalamus, which is located at the base of the brain along the optic nerve margin and typically 3 mm deep, was collected.…”

Section: Methodsmentioning

confidence: 99%

Intracerebroventricular Injection of Metformin Induces Anorexia in Rats

et al. 2012

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BackgroundMetformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.MethodsTo evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.ResultsAn ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.ConclusionOur results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.

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Section: Methodsmentioning

confidence: 99%

Intracerebroventricular Injection of Metformin Induces Anorexia in Rats

et al. 2012

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“…Multiple-day intraperitoneal administration of 1 decreases body weight to a greater extent in DIO mice than in chow-fed controls. 33 Similarly, studies in genetic 22 and diet-induced obese rats 34 and in hypothalamic lesioned models 35 have also shown increased sensitivity to 1 or R-MSH. With peripheral administration, the issue arises of whether the effect is that a greater dose is given when drug administration is normalized to total body weight instead of to lean (metabolically active) body mass.…”

Section: Pharmacology Of Melanocortin Peptidesmentioning

confidence: 98%

Melanocortin-4 Receptor (MC4R) Agonists for the Treatment of Obesity

2006

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“…Glutamate, the major excitatory neurotransmitter in the brain, is also categorized as an excitotoxin (Segura-Aguilar and Kostrzewa, 2004). It leads to degeneration of the neurons in the arcuate nucleus, inner retinal layers and various other brain areas (Kubo et al, 1993;Ishikawa et al, 1997;Beas-Zarate et al, 2002;Tamas et al, 2004;Babai et al, 2005;, along with endocrinological, neurochemical and circadian alterations (Dawson and Lorden, 1981;Miyabo et al, 1985;Frieder and Grimm, 1987;Mistlberger and Antle, 1999;Urena-Guerrero et al, 2003;Kim et al, 2005). However, administration of MSG to neonatal rodents brings about several profound changes.…”

Section: Introductionmentioning

confidence: 99%

Changes in open-field activity and novelty-seeking behavior in periadolescent rats neonatally treated with monosodium glutamate

et al. 2007

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Monosodium glutamate (MSG) treatment of neonatal rodents leads to degeneration of the neurons in the arcuate nucleus, inner retinal layers and various other brain areas. It also causes various changes in the motor activity, sensory performance and learning abilities. We have previously shown that MSG treatment delays the appearance of some reflexes during neurobehavioral development and leads to temporary changes in reflex performance and motor coordination. Investigation of novelty-seeking behavior is of growing importance for its relationship with sensitivity to psychomotor stimulants. Perinatal administration of numerous toxic agents has been shown to influence novelty-seeking behavior in rats, but little is known about the influence of neonatal MSG treatment on the novelty-seeking behavior. The aim of the present study was to compare changes in locomotor, spontaneous exploratory and novelty-seeking behavior in periadolescent rats neonatally treated with MSG. Newborn rats were treated with 4 mg/g MSG subcutaneously on postnatal days 1, 3, 5, 7 and 9. Open-field behavior was tested at 2, 3, 4, 6 and 8 weeks of age. We found that MSG administration led to only temporary increases in locomotor behavior, which was more pronounced during the first few postnatal weeks, followed by a subtle hypoactivity at 2 months of age. Novelty-seeking was tested in four 5-min trials at 3 weeks of age. Trial 1 was in an empty open-field, two identical objects were placed in the arena during trial 2 and 3, and one of them was replaced to a novel object during trial 4. We found that the behavioral pattern of MSG-treated rats was the opposite in all tested signs in the novelty exploration test compared to control pups. In summary, our present study shows that neonatal MSG treatment leads to early temporary changes in the locomotor activity followed by hypoactivity at 2 months of age. Furthermore, MSG-treated rats show a markedly disturbed novelty-seeking behavior represented by altered activity when subjected to a novel object.

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Leptin-like effects of MTII are augmented in MSG-obese rats

Cited by 25 publications

References 27 publications

Intracerebroventricular Injection of Metformin Induces Anorexia in Rats

Intracerebroventricular Injection of Metformin Induces Anorexia in Rats

Melanocortin-4 Receptor (MC4R) Agonists for the Treatment of Obesity

Changes in open-field activity and novelty-seeking behavior in periadolescent rats neonatally treated with monosodium glutamate

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