Differential Effects of Recombinant Adeno-Associated Virus-Mediated Neuropeptide Y Overexpression in the Hypothalamic Paraventricular Nucleus and Lateral Hypothalamus on Feeding Behavior

Tiesjema, Birgitte; Adan, Roger A.H.; Luijendijk, Mieneke C. M.; Kalsbeek, Andries; Fleur, Susanne E. la

doi:10.1523/jneurosci.3280-07.2007

Cited by 62 publications

(59 citation statements)

References 39 publications

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“…Levels of hypothalamic NPY are indicative of nutritional status; NPY mRNA content and NPY release increase during fasting and decrease after refeeding (Sanacora et al, 1990;Swart et al, 2001Swart et al, , 2002. Furthermore, increased NPY levels precede hyperphagia (Brady et al, 1990;Sahu et al, 1997;Tiesjema et al, 2007Tiesjema et al, , 2009. Direct pharmacological evidence of the orexigenic effects of NPY are provided by studies demonstrating that its intracerebroventricular administration (Clark et al, 1984;Levine and Morley, 1984;Semjonous et al, 2009) or its direct administration into FIG.…”

Section: Arcuate Nucleus Orexigenic Neuropeptide Y/agouti-related Pepmentioning

confidence: 99%

Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite

2010

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Section: Arcuate Nucleus Orexigenic Neuropeptide Y/agouti-related Pepmentioning

confidence: 99%

Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite

2010

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“…We investigated whether knockdown of Socs3 mRNA in the MBH had any effects on mRNA expression levels of Agrp, Npy, and Pomc, because leptin signaling is suggested to regulate transcription of these neuropeptides. In addition, the observed phenotype, reduced locomotor activity, and increased feeding in the light phase resemble that of increased NPY signaling (Tiesjema et al 2007). Radioactive ISH showed that AAV-sh-1 rats had significantly increased levels of Npy in the Arc compared with AAV-sh-c rats (Fig.…”

Section: Effects Of Socs3 Knockdown On Endocrine Parameters and Body mentioning

confidence: 83%

“…The increased levels of Npy mRNA that we observed may explain the unexpected effects on body weight, food intake, fat mass, and locomotor activity after Socs3 knockdown in the MBH. Viral vector-mediated Npy overexpression in several hypothalamic regions results in increased body weight, decreased locomotor activity in the dark period, and increased food intake, in particular, in the light period (Tiesjema et al 2007, Yang et al 2009). In addition, acute i.c.v.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, overexpression of Npy in the PVN (a target area for NPY neurons located in the Arc) was reported to only temporarily increase food intake due to compensatory mechanisms (Tiesjema et al 2007(Tiesjema et al , 2009). The reduced locomotor activity that we observed in the dark period of days 27-29 and 48-50 is not likely due to unspecific illness.…”

Section: Discussionmentioning

confidence: 99%

“…The reduction in locomotor activity is in agreement with both Npy overexpression studies and i.c.v. administration studies that show a long-term decrease in locomotor activity (Heilig & Murison 1987, Heilig et al 1989, Tiesjema et al 2007). Since we expected that rats with unilateral knockdown of Socs3 in the MBH would show similar features as those with bilateral knockdown, we also examined the effects on locomotor activity, fat mass, and leptin concentration in these rats.…”

Section: Discussionmentioning

confidence: 99%

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Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus: counterintuitive effects on energy balance

Backer

Brans

Rozen

et al. 2010

Journal of Molecular Endocrinology

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An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was downregulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.

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Autonomic Regulation of Hepatic Glucose Production

Bisschop

Fliers

Kalsbeek

2014

Comprehensive Physiology

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Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system to communicate with peripheral organs. Within the brain, the hypothalamus is the key region to integrate signals on energy status, including signals from lipid, glucose, and hormone sensing cells, with afferent neural signals from the internal and external milieu. In turn, the hypothalamus regulates metabolism in peripheral organs, including the liver, not only via the anterior pituitary gland but also via multiple neuropeptidergic pathways in the hypothalamus that have been identified as regulators of hepatic glucose metabolism. These pathways comprise preautonomic neurons projecting to nuclei in the brain stem and spinal cord, which relay signals from the hypothalamus to the liver via the autonomic nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are not separate entities. They appear to act as a single integrated regulatory system, far more subtle, and complex than when each is viewed in isolation. Consequently, hypothalamic regulation should be viewed as a summation of both neuroendocrine and neural influences. As a result, our endocrine-based understanding of diseases such as diabetes and obesity should be expanded by integration of neural inputs into our concept of the pathophysiological process.

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Differential Effects of Recombinant Adeno-Associated Virus-Mediated Neuropeptide Y Overexpression in the Hypothalamic Paraventricular Nucleus and Lateral Hypothalamus on Feeding Behavior

Cited by 62 publications

References 39 publications

Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite

Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite

Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus: counterintuitive effects on energy balance

Autonomic Regulation of Hepatic Glucose Production

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