Shah M, Vella A (2014) Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord 15(3):181-187. doi: 10.1007/s11154-014-9289-5 PMID: 24811133

Objective: To determine if the synergistic actions of GLP-1 in the gut and brain, acting on both central and peripheral receptors are responsible for the effects of the hormone on satiety.

Summary: The effect of GLP-1 on satiety is primarily derived from its action on anorexigenic hormones so that when NPY/ AgRP neurons are specifically eliminated by NPY-SAP, the effect of GLP-1 on decreasing satiation persists.

Related Products: NPY-SAP (Cat. #IT-28)

See Also:

• Bugarith K et al. Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Endocrinology 146(3):1179-1191, 2005.

Donahue RR, Corder GF, Mcnamara KC, Wiley RG, Taylor BK (2011) Transmission of neuropathic pain by spinal neurons expressing the NPY Y1 receptor. Neuroscience 2011 Abstracts 179.16. Society for Neuroscience, Washington, DC.

Summary: Endogenous neuropeptide Y (NPY) acts at Y receptors in the dorsal spinal cord to exert a tonic inhibitory control of chronic allodynia (Solway et al, PNAS 108:7224-9, 2011). In this and the adjacent presentation, we tested the hypothesis that NPY does this by inhibiting Y1 receptors on pain transmission neurons or on central terminals of primary afferent neurons. We selectively lesioned cells expressing the NPY receptors in the dorsal horn with intrathecal administration of the NPY-conjugated ribosomal toxin, NPY-saporin. NPY-saporin significantly reduced the population of Y1 receptors in the lumbar dorsal horn by over 50%. Neither NK1 receptors in the dorsal horn, nor neuronal counts in the DRG were affected, suggesting a specific effect on Y1+, NK1- neurons in the dorsal horn, while sparing Y1+ central presynaptic terminals. Fourteen days later, we ligated the tibial and common peroneal branches of the sciatic nerve (spared nerve injury, SNI), and evaluated the development of allodynia and hyperalgesia on post-SNI days 1, 3, 5, 7, 14, 21, 28, 35, and 42. When compared to saporin controls, NPY-saporin (1000 ng) decreased mechanical allodynia (von Frey threshold), cold allodynia (paw withdrawal response to application of a drop of acetone) and mechanical hyperalgesia (paw response to blunt pin). This effect began three days after SNI and lasted until forty two days after SNI. When injected in uninjured rats, NPY-saporin did not disrupt motor coordination (accelerating rotarod), baseline heat or mechanical thresholds, or animal activity levels. We conclude that Y1-expressing cells in the dorsal horn exert a tonic facilitatory control of neuropathic pain, and partially mediate the inhibitory actions of NPY.

Related Products: NPY-SAP (Cat. #IT-28)

Wiater MF, Mukherjee S, Li AJ, Dinh TT, Rooney EM, Simasko SM, Ritter S (2011) Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus. Am J Physiol Regul Integr Comp Physiol 301(5):R1569-R1583. doi: 10.1152/ajpregu.00168.2011 PMID: 21880863

Summary: Feeding and sleep/wake states interact rhythmically across the circadian cycle. It is suspected that the mediobasal hypothalamic area (MBH) is the site where these rhythms are integrated. The authors administered bilateral 24-ng injections of NPY-SAP (Cat. #IT-28) into the arcuate nucleus in order to eliminate NPY receptor-expressing neurons in the MBH of rats. Blank-SAP (Cat. #IT-21) was used as a control. The results indicate that these neurons are required for the interaction of feeding and sleep/wake timing.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Read More.

Bartness TJ, Keen-Rhinehart E, Dailey MJ, Teubner BJ (2011) Neural and hormonal control of food hoarding. Am J Physiol Regul Integr Comp Physiol 301(3):R641-R655. doi: 10.1152/ajpregu.00137.2011

Summary: Hoarding of food is a commonly found behavior in humans and animals. This review discusses the neuronal and hormonal processes involved in the control of food hoarding. Several aspects of food hoarding are examined, including the role of food deprivation, environment, levels of hormones like leptin, ghrelin, and levels of peptides such as cholecystokinin. One experiment discussed injected NPY-SAP (Cat. #IT-28) into the arcuate nucleus of rats, which changed food hoarding responses to deprivation.

Related Products: NPY-SAP (Cat. #IT-28)

Wiater MF, Mukherjee S, Dinh TT, Rooney E, Li A-J, Simasko SM, Ritter S (2010) The arcuate nucleus of the hypothalamus controls the circadian distribution of sleep and feeding. Neuroscience 2010 Abstracts 648.16/H17. Society for Neuroscience, San Diego, CA.

Summary: Integration of daily sleep and feeding rhythms is incompletely understood. We examined the role of the hypothalamic arcuate nucleus (Arc) in these processes using Arc microinjections of the targeted toxin, NPY-saporin (NPY-SAP), or control blank-saporin (B-SAP). NPY-sap targets and destroys NPY receptor-expressing neurons. We monitored 24 hr feeding over a 30-day period beginning 2 wks after the Arc injections, and used EEG recordings to assign vigilance states. Vigilance was divided into rapid-eye movement sleep (REMS), non-REMS (NREMS) and wake. NPY-SAP lesioned rats were hyperphagic , consuming up to 225% of pre-injection baseline. They rapidly became obese. While in the sleep-monitoring chambers, their body weight change per week ranged from 56 ± 9 g to 40.5 ± 4.5g, compared to 6 ± 0.4 g/wk for B-SAP rats. Their circadian pattern of food intake was severely disrupted, such that intake in light and dark periods were approximately equal (43% of their total intake was consumed in the light period vs. 25% in B-SAP controls). Sleep patterns were also significantly disrupted in the NPY-SAP animals. The occurrence of rapid eye movement sleep (REMS) was inverted in phase, occurring mainly at night, rather than during the day. NonREMS was distributed equally across day and night, instead of occurring predominantly during the day. However, 24-hr total REMS and NREMS time was normal. B-SAP controls had normal sleep patterns, with NREMS and REMS occurring predominantly in the light phase. To determine if the change in sleep pattern was due to the change in feeding patterns, we restricted access to food to the dark period for 4 days. NPY-SAP treated animals doubled their food intake in the dark period. However, sleep patterns were not changed compared to the ad libitum feeding period in either NPY-SAP or B-SAP rats. After 7 days of ad libitum feeding, we restricted food access to the light period for 4 days. Again, NPY-SAP animals doubled their intake during the feeding period, this time during the light phase, and sleep patterns were not changed in either group by the restricted feeding. By 100 days post-lesion, the NPY-sap animals were still obese, but the patterning and amount of their food intake were becoming similar to controls. However, when evaluated again, sleep patterns were still altered to the same degree as observed early post-lesion. These results confirm the importance of NPY-receptive Arc neurons in controlling food intake. They also reveal an unexpected role for the Arc in the timing of both NREMS and REMS that appears to be independent of the patterning of food intake.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Lemons LL, Chatterjee K, Wiley RG (2010) Neuropeptide receptor co-expression in superficial dorsal horn: Effects of galanin-saporin, neuropeptide y-saporin and dermorphin-saporin. Neuroscience 2010 Abstracts 585.5/XX19. Society for Neuroscience, San Diego, CA.

Summary: We have previously shown that the role of specific neurons in behavioral processes can be fruitfully studied using targeted toxins. Toxins composed of a targeting neuropeptide coupled to the ribosomal-inactivating toxin, saporin, are used to selectively destroy superficial dorsal horn neurons expressing the cognate peptide receptors followed by assessment of changes in pain behavior. In the present study, we sought to compare the anatomic effects of three closely related targeted toxins, each with different nocifensive behavioral effects. Rats were given single lumbar intrathecal injections of either galanin-saporin (Gal-SAP), neuropeptide Y-saporin (NPY-SAP), or dermorphin-saporin (Derm-SAP). Lumbar spinal cord sections from each rat were stained for each of the three receptors, GalR-1, Y1R and MOR (mu opiate) using standard immunoperoxidase technique. Each toxin produced a significant decrease in staining for its cognate receptor. Gal-SAP animals showed no change in either MOR or Y1R staining. NPY-SAP rats showed decreased staining for both GalR1 and MOR, and Derm-SAP rats were assessed for changes in expression of GalR1 and Y1R. These findings suggest overlaps between the populations of neurons that express the GalR1, Y1R, and MOR. Specifically, Y1R-expressing neurons also express GalR1 and MOR, probably by separate subpopulations of Y1R neurons. The results also suggest either that Gal-SAP only kills neurons that do not express either of the other two receptors, or some of the observed loss of receptors after NPY-SAP is due to secondary (transsynaptic) effects. Double- and triple-label fluorescent immunohistochemistry will be used to directly visualize receptor co-expression patterns and targeted toxin effects. These results will be valuable in interpreting the unique nocifensive behavioral effects of each of these targeted toxins.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Galanin-SAP (Cat. #IT-34), NPY-SAP (Cat. #IT-28)

Lyons AM, Thiele TE (2010) Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice. Peptides 31(12):2193-2199. doi: 10.1016/j.peptides.2010.09.009

Summary: Neuropeptide Y (NPY) in the hypothalamus is known to modulate feeding behavior. In this work the authors used bilateral 48 ng injections of NPY-SAP (Cat. #IT-28) into the central amygdala or basomedial hypothalamus (BMH) of rats to investigate the role of NPY in anxiety. Blank-SAP (Cat. #IT-21) was used as a control. Injections into the amygdala increased anxiety-like behavior, while injections into the BMH reduced anxiety-like behavior. BMH injections also initiated an increase of NPY-1 receptor expression in the basolateral nuclei of the amygdala.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Dailey MJ, Bartness TJ (2010) Arcuate nucleus destruction does not block food deprivation-induced increases in food foraging and hoarding. Brain Res 1323:94-108. doi: 10.1016/j.brainres.2010.01.078

Summary: While some aspects of food intake are understood, mechanisms controlling hoarding of food have not been identified. This work investigates the role of NPY in the arcuate nucleus (Arc) in hoarding. Siberian hamsters received 48 ng injections of NPY-SAP (Cat. #IT-28) into the Arc; blank-SAP (Cat. #IT-21) was used as a control. In lesioned animals food deprivation-induced hoarding was increased 100%, but baseline foraging and food hoarding was unchanged.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Li A-J, Wang Q, Dinh TT, Ritter S (2009) Leptin-saporin injection into the arcuate nucleus lesions NPY/AGRP and POMC neurons and produces hyperphagia, obesity and changes in diurnal feeding patterns in rats. Neuroscience 2009 Abstracts 374.5/EE116. Society for Neuroscience, Chicago, IL.

Summary: Leptin-saporin (Lep-SAP), a conjugate of leptin with a ribosomal inactivating toxin, saporin (Advanced Targeting Systems), is a novel toxin designed to destroy leptin receptor-expressing cells selectively in vitro. However, its lesioning properties in vivo are currently unknown. Here, we injected Lep-SAP into the arcuate nucleus (Arc), to examine its effects on feeding behavior and on leptin receptor-expressing NPY/AGRP and POMC neurons in this area. Immunohistochemical studies showed unilateral injection of Lep-SAP into the Arc dramatically reduced numbers of NPY-Y1- and α-MSH- positive neurons compared to the contralateral side injected with SAP control. Real-time PCR revealed only 11-21% of Agrp and Pomc expression remaining in the Arc after Lep-SAP injection into this region. Rats injected bilaterally with Lep-SAP were unresponsive to central leptin administration and showed dramatic increases in feeding, body weight and light-phase feeding, compared pre-injection baseline. Two weeks after injection, total daily feeding was increased by 75%, light phase feeding by 359% and dark phase feeding by 33%. Control SAP injections did not produce these changes. Clock gene expression in homogenates of whole hypothalamus and liver were quantified at ZT 5-7. Bmal1 expression in hypothalamus and liver of Lep-SAP rats was decreased, while hepatic Per1 expression was increased compared to control. Results demonstrate that Lep-SAP effectively lesions Arc leptin receptor-expressing NPY/AGRP and POMC neurons in vivo, and that rats with this lesion are hyperphagic and obese, possibly due to enhanced hunger drive, lack of responsiveness to leptin and/or changes in circadian control of feeding behavior.

Related Products: NPY-SAP (Cat. #IT-28), Leptin-SAP (Cat. #IT-47)

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Wiley RG, Lemons LL, Kline IV RH (2009) Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience 161:139-147. doi: 10.1016/j.neuroscience.2008.12.017

Summary: This work examines the effect of lumbar intrathecal administration of NPY-SAP (Cat. #IT-28), and the role of Y1 NPY receptor-expressing neurons (Y1R) in response to thermal and chemical stimulation. Rats received 500 ng or 750 ng intrathecal injections of NPY-SAP. Blank-SAP (Cat. #IT-21) was used as a control. Lesioned animals displayed a specific loss of Y1R in the dorsal horn, as well as reduced nocifensive reflex responses.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)