A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice.

Proceedings of the National Academy of Sciences of the United States of America
Akane IshiharaTakehiro Fukami

Abstract

Neuropeptide Y (NPY) is thought to have a major role in the physiological control of energy homeostasis. Among five NPY receptors described, the NPY Y5 receptor (Y5R) is a prime candidate to mediate some of the effects of NPY on energy homeostasis, although its role in physiologically relevant rodent obesity models remains poorly defined. We examined the effect of a potent and highly selective Y5R antagonist in rodent obesity and dietary models. The Y5R antagonist selectively ameliorated diet-induced obesity (DIO) in rodents by suppressing body weight gain and adiposity while improving the DIO-associated hyperinsulinemia. The compound did not affect the body weight of lean mice fed a regular diet or genetically obese leptin receptor-deficient mice or rats, despite similarly high brain Y5R receptor occupancy. The Y5R antagonist acts in a mechanism-based manner, as the compound did not affect DIO of Y5R-deficient mice. These results indicate that Y5R is involved in the regulation and development of DIO and suggest utility for Y5R antagonists in the treatment of obesity.

References

Sep 1, 1992·Brain Research. Molecular Brain Research·A SahuS P Kalra
Jan 1, 1989·The Medical Clinics of North America·E A Sims
Feb 1, 1994·The American Journal of Clinical Nutrition·A AstrupN J Christensen
Feb 1, 1997·The Journal of Clinical Investigation·M Van HeekH R Davis
Jul 1, 1997·Trends in Neurosciences·A G Blomqvist, H Herzog
Jun 20, 1998·Science·J O Hill, J C Peters
Jun 12, 1998·Nature Medicine·D J MarshR D Palmiter
Dec 17, 1998·The Journal of Clinical Investigation·L CriscioneN Levens
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·A KushiM Nakamura
Jun 29, 2000·Biochemical and Biophysical Research Communications·A KanataniM Ihara
Jul 13, 2000·The British Journal of Nutrition·P Arner
Mar 13, 2001·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·O Della ZuanaN Levens
Jun 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Amanda SainsburyHerbert Herzog
Aug 9, 2002·Nature·Rachel L BatterhamStephen R Bloom
Sep 25, 2003·Bioorganic & Medicinal Chemistry Letters·Richard L ElliottJames V Cassella

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Citations

Mar 1, 2012·Psychopharmacology·Gunnar SørensenDavid P D Woldbye
Jun 29, 2010·Journal of Molecular Neuroscience : MN·Shinjae ChungOlivier Civelli
Mar 18, 2004·Bioorganic & Medicinal Chemistry Letters·Nagaaki SatoTakehiro Fukami
Mar 23, 2012·Chemical Reviews·Alexander DömlingKan Wang
May 31, 2002·Chemical & Pharmaceutical Bulletin·Sébastien GuéryJean-Albert Boutin
Sep 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ryo YoshimotoShigeru Tokita
Mar 7, 2008·Expert Opinion on Investigational Drugs·Tung M Fong
Jun 2, 2009·European Journal of Pharmacology·Satoshi MashikoAkio Kanatani
May 8, 2009·Physiology & Behavior·Sharon R Ladyman, Barbara Woodside
May 7, 2011·British Journal of Pharmacology·Ernie YulyaningsihAmanda Sainsbury
Apr 2, 2010·American Journal of Medical Genetics. Part a·Andreas TzschachVera Kalscheuer
Feb 21, 2008·Nutritional Neuroscience·Bernard BeckAlain Stricker-Krongrad
Mar 29, 2011·Pharmacology & Therapeutics·Lei ZhangHerbert Herzog
Dec 19, 2018·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Seongjoon ParkIsao Shimokawa
Jul 23, 2008·Developmental Disabilities Research Reviews·Jason C G Halford, Joanne A Harrold
Sep 6, 2007·Endocrine Reviews·M M Kamiji, A Inui
May 18, 2006·American Journal of Physiology. Renal Physiology·Yuehan ZhouWalter F Boron
May 11, 2006·American Journal of Physiology. Renal Physiology·Colin FriedrichKarlhans Endlich
Oct 29, 2011·Biomedical Research·Ken-Ichi NakajimaYoshinori Marunaka
Sep 11, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Seongjoon ParkIsao Shimokawa
May 19, 2011·Endocrinology·Andrea M PeierDonald J Marsh
Oct 5, 2016·International Journal of Obesity : Journal of the International Association for the Study of Obesity·M MuenznerT Walther

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