The neuropeptide Y-ergic system: potential therapeutic target against bone loss with obesity treatments

Abstract

Obesity is no longer considered to provide protection against osteoporosis. Moreover, treatments for obesity are now suspected of reducing bone mass. With the escalating incidence of obesity, combined with increases in the frequency, duration and intensity of interventions used to combat it, we face a potential increase in health burden due to osteoporotic fractures. The neuropeptide Y-ergic system offers a potential target for the prevention and anabolic treatment of bone loss in obesity, due to its dual role in the regulation of energy homeostasis and bone mass. Although the strongest stimulation of bone mass by this system appears to occur via indirect hypothalamic pathways involving Y2 receptors (one of the five types of receptors for neuropeptide Y), Y1 receptors on osteoblasts (bone-forming cells) induce direct effects to enhance bone mass. This latter pathway may offer a suitable target for anti-osteoporotic treatment while also minimizing the risk of adverse side effects.

Keywords:

• bariatric surgery
• bone mineral density
• bone turnover
• caloric restriction
• diet, reducing
• energy restriction
• neuropeptide Y
• obesity
• peptide YY
• Y receptors

Financial & competing interests disclosure

This study was supported by the National Health and Medical Research Council (NHMRC) of Australia via an Early Career Research Fellowship to RV Seimon, a Postgraduate Scholarship to AD Nguyen, and a research project grant and Senior Research Fellowship to A Sainsbury. The authors are also grateful to the Endocrine Society of Australia for a Postdoctoral Award to RV Seimon. A Sainsbury has received payment from Eli Lilly, the Pharmacy Guild of Australia and Novo Nordisk for seminar presentation at conferences. She is also the author of the Don’t Go Hungry Diet (Bantam, Australia and New Zealand, 2007) and Don’t Go Hungry For Life (Bantam, Australia and New Zealand, 2011). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Obesity is increasingly recognized as being detrimental to skeletal health.

• Obesity treatments – namely bariatric surgery and possibly also diet-induced weight loss – may further compromise skeletal health in obese individual by increasing bone turnover and reducing bone mass.

• Animal research indicates that bone loss with human obesity treatments could conceivably be mediated by increased hypothalamic neuropeptide Y-ergic activity, notably via actions on hypothalamic Y2 receptors.

• Targeting hypothalamic Y2 receptors as a strategy to combat bone loss during obesity treatments, as with any therapy targeted to the central nervous system, is likely to be fraught with undesirable side effects.

• Targeting Y1 receptors on osteoblasts (bone-forming cells) may offer a suitable strategy for preventing and reversing bone loss in response to obesity treatments or other triggers for bone loss, provided that androgen sufficiency prevails.

Notes