The role of diet in health and diseases related to muscle and bone has been an area of active study. Recently, endocannabinoids (EC), endogenous derivatives of arachidonic acid, an omega-6 (n-6) polyunsaturated fatty acid (PUFA), have been discovered to play regulatory roles in bone mass and muscle energy metabolism.

This signaling system consists of the G-protein coupled cannabinoid receptors, CB1 and CB2, expressed in central and peripheral tissues and cells, which are variably activated by the production and on demand release of endogenous and synthetic agonists and antagonists.

We propose that the balance between omega-6 and omega-3 (n-3) PUFA is an important modifier for the activation and suppression of endocannabinoid receptors and therefore, downstream signaling actions in cells.

The potential of dietary PUFA to regulate this signaling system to influence the metabolic and physiological outcomes favorable to musculoskeletal health is the purpose of this review.

The important role of n-3 PUFA in metabolic and physiological processes that attenuate muscle and bone loss under conditions of disease and stress is one aspect described herein.

In this review, we
1. first introduce the EC agonists (ligands) and their receptors (CB1 and CB2) and the general actions of EC signaling in various organs and systems.
2. Second, we describe EC signaling in bone and muscle and how dietary PUFA influence the levels of endogenous agonists.
3. Third, we discuss the potential implications of how dietary PUFA impact this system to minimize muscle atrophy and osteopenia and support healthy muscle development and bone modeling.