Cannabinoids Excite Hypothalamic Melanin-Concentrating Hormone But Inhibit Hypocretin/Orexin Neurons: Implications for Cannabinoid Actions on Food Intake and Cognitive Arousal

Huang, Hao; Acuña-Goycolea, Claudio; Liu, Ying; Cheng, Hai-Ying Mary; Obrietan, Karl; Pol, Anthony N. van den

doi:10.1523/jneurosci.0732-07.2007

Cited by 98 publications

(90 citation statements)

References 70 publications

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“…In line with body weight changes, there was a significant effect of time (baseline and day 26 of treatment) on fat mass (F (1,19) ¼ 8.54, P ¼ 0.009) and a strong interaction between treatment group and time (F (1,19) ¼ 32.51, P < 0.001) though the between-group effects on fat mass did not reach a statistically significant level (F (1,19) ¼ 0.99, P ¼ 0.331) again showing that fat mass had declined in the treatment group over time but not in the controls ( Figure 1C). After 26 days of MCHR1 antagonist treatment there was a significant decrease in fat mass (Paired t test: t ¼ 5.43, df ¼ 9, P < 0.001) whereas vehicle-treated mice showed no significant change in fat mass (Paired t test: t ¼ -2.23, df ¼ 10, P ¼ 0.05).…”

Section: Body Mass and Fatnessmentioning

confidence: 73%

“…There were no significant differences between vehicle-treated and MCHR1 antagonist-treated groups in glucose tolerance (F (1,19) ¼ 0.36, P ¼ 0.558, Figure 2A). However, age-matched non-DIO mice that were fed with a regular diet exhibited a better tolerance to glucose, suggesting that HFD impaired glucose metabolism (Figure 2A).…”

Section: Glucose Tolerance and Plasma Metabolitesmentioning

confidence: 93%

“…Plasma leptin levels were highly associated with body fat mass (R 2 ¼ 0.94, F (1,19) ¼ 290.09, P < 0.001, Figure 2B). Despite an absolute difference in leptin (Independent t test: t ¼ 2.48, df ¼ 19, P ¼ 0.022; Figure 2C), chronic MCHR1 antagonist treatment had no FIGURE 1 Chronic administration of a MCHR1 antagonist decreased body mass and fatness in DIO mice.…”

Section: Glucose Tolerance and Plasma Metabolitesmentioning

confidence: 97%

“…Cumulative food intake was significantly reduced by chronic MCHR1 antagonist administration (GLM repeated measures: group: F ¼ 7.121, P ¼ 0.015, days of treatment, F (1,19) ¼ 1638.26, P < 0.001, days of treatment Â group, F (1,19) ¼ 4.559, P < 0.001; Figure 3B). Over the 30-day treatment, accumulated food intake of DIO mice receiving the MCHR1 antagonist was 9.1% less than that of vehicle-treated counterparts (t test: t ¼ 2.14, df ¼ 19, P ¼ 0.046).…”

Section: Food Intake and Energy Budgetmentioning

confidence: 99%

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Effects of a specific MCHR1 antagonist (GW803430) on energy budget and glucose metabolism in diet‐induced obese mice

Zhang

Sinclair

Selman

et al. 2013

Obesity

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Objective: The melanin-concentrating hormone (MCH) is a centrally acting peptide implicated in the regulation of energy homeostasis and body weight, although its role in glucose homeostasis is uncertain. Our objective was to determine effects of MCHR1 antagonism on energy budgets and glucose homeostasis in mice. Methods: Effects of chronic oral administration of a specific MCHR1 antagonist (GW803430) on energy budgets and glucose homeostasis in diet-induced obese (DIO) C57BL/6J mice were examined. Results: Oral administration of GW803430 for 30 days reduced food intake, body weight, and body fat. Circulating leptin and triglycerides were reduced but insulin and nonesterified fatty acids were unaffected. Despite weight loss there was no improvement in glucose homeostasis (insulin levels and intraperitoneal glucose tolerance tests). On day 4-6, mice receiving MCHR1 antagonist exhibited decreased metabolisable energy intake and increased daily energy expenditure. However these effects had disappeared by day 22-24. Physical activity during the dark phase was increased by MCHR1 antagonist treatment throughout the 30-day treatment. Conclusions: GW803430 produced a persistent anti-obesity effect due to both a decrease in energy intake and an increase in energy expenditure via physical activity but did not improve glucose homeostasis.

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Section: Body Mass and Fatnessmentioning

confidence: 73%

Section: Glucose Tolerance and Plasma Metabolitesmentioning

confidence: 93%

Section: Glucose Tolerance and Plasma Metabolitesmentioning

confidence: 97%

Section: Food Intake and Energy Budgetmentioning

confidence: 99%

See 2 more Smart Citations

Effects of a specific MCHR1 antagonist (GW803430) on energy budget and glucose metabolism in diet‐induced obese mice

Zhang

Sinclair

Selman

et al. 2013

Obesity

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“…27 Owing to its localization on inhibitory and excitatory presynaptic terminals, retrograde activation of CB 1 receptors can regulate the release and/or signaling of several neurotransmitters and neuropeptides, including DA, 30 MCH and orexin. 31 Recent findings of Cristino and Di Marzo show that orexin neurons express a biosynthetic enzyme for 2-arachidonoylglycerol and show that CB 1 receptors are localized on GABAergic fibers that surround orexin neurons (see Matias et al 32 ). These authors also observe that orexin-1 and CB 1 receptors are highly colocalized in the hypothalamus, 32 whereas others have shown that CB 1 activation can sensitize orexin-1 receptors expressed in the same cell through receptor-receptor functional interactions.…”

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confidence: 99%

Neurosystems linking corticolimbic and hypothalamic pathways in energy balance: view from the Chair

Fulton

2009

Int J Obes

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Recent work has advanced our knowledge of the neural pathways interfacing corticolimbic substrates of food motivation and reward with hypothalamic controls of food intake. As a neuroanatomical interface between limbic motivational processes, energy-sensing mechanisms in the mediobasal hypothalamus and motor output pathways, several studies draw attention to the lateral hypothalamus. Reviewed here are some highlights of the first session of the 11th International Symposium of the Merck- Keywords: dopamine; endocannabinoids; nucleus accumbens; orexin; melanin-concentrating hormoneThe central nervous system plays a crucial role in integrating numerous hormonal and metabolic signals derived from the periphery and thereby generating adaptive behavioral responses to changing energy demands. Under normal conditions, there are several mechanisms at the level of the hypothalamus and hindbrain that effectively respond to states of energy deficit or surplus in part by modulating appetite. The significance of key hypothalamic neuronal populations for energy homeostasis is underscored by genetic gain-and loss-function studies. 1 On the other hand, there exist cortical and limbic processes that underlie the cognitive and rewarding aspects of food by assimilating information about taste, texture, smell and post-ingestive consequences. 2,3 Sensory and value representations of food and the cues and properties associated with obtaining food are stored in the memory where they serve an essential function, especially during conditions of low food availability, to orient animals back to (or away from in conditions of aversion) the source of food.The heightened behavioral, emotional and cognitive response to palatable high-fat and -sugar foods that has evolved can be understood in terms of what these foods offer in energy value. Indeed, the rewarding experience that is produced by eating tasty, energy-rich foods can produce a lasting impression that acts to strengthen action-outcome associations and reinforce future behavior directed at obtaining food. Of relevance for the epidemiology of obesity in humans, we must consider that food intake is accompanied by several precipitating factors in modern industrialized societies. Many foods come in catchy packaging, are well advertised, easily obtainable and relatively cheap. Thus, we are frequently bombarded with food-associated cues that remind us about how, where and when we can get access to these foods. As we have become well acquainted with the contribution of rewarding, easily accessible and inexpensive high-fat and -sugar foods to the epidemic of obesity, it is increasingly evident that we need to unravel the neural mechanisms that process not only the hedonic effects of palatable foods, but also those that govern reward-relevant learning, valuation and decision making in the context of modern social and economic climates.Of direct bearing to the discussion here, it is important that we identify which neural pathways and processes interface corticolimbic mechanisms affecting feeding...

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Endocannabinoids and energy homeostasis: An update

Cristino¹,

Becker

Marzo³

2014

BioFactors

107

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The endocannabinoid system (ECS) is a widespread intercellular signaling system that plays a critical role in energy homeostasis, meant as the precise matching of caloric intake with energy expenditure which normally keeps body weight stable over time. Complex interactions between environmental and neurohormonal systems directly contribute to the balance of energy homeostasis. This review highlights established and more recent data on the brain circuits in which the ECS plays an important regulatory role, with focus on the hypothalamus, a region where numerous interacting systems regulating feeding, satiety, stress, and other motivational states coexist. Although not meant as an exhaustive review of the field, this article will discuss how endocannabinoid tone, in addition to reinforcing reward circuitries and modulating food intake and the salience of food, controls lipid and glucose metabolism in several peripheral organs, particularly the liver and adipose tissue. Direct actions in the skeletal muscle and pancreas are also emerging and are briefly discussed. This review provides new perspectives into endocannabinoid control of the neurochemical causes and consequences of energy homeostasis imbalance, a knowledge that might lead to new potential treatments for obesity and related morbidities.

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Cannabinoids Excite Hypothalamic Melanin-Concentrating Hormone But Inhibit Hypocretin/Orexin Neurons: Implications for Cannabinoid Actions on Food Intake and Cognitive Arousal

Cited by 98 publications

References 70 publications

Effects of a specific MCHR1 antagonist (GW803430) on energy budget and glucose metabolism in diet‐induced obese mice

Effects of a specific MCHR1 antagonist (GW803430) on energy budget and glucose metabolism in diet‐induced obese mice

Neurosystems linking corticolimbic and hypothalamic pathways in energy balance: view from the Chair

Endocannabinoids and energy homeostasis: An update

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