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Lakes of the Four Seasons, IN, United States

Watkins B.A.,Lipid Chemistry and Molecular Biology Laboratory | Watkins B.A.,Lafayette College | Watkins B.A.,Indiana University | Hutchins H.,Lipid Chemistry and Molecular Biology Laboratory | And 2 more authors.
Journal of Nutritional Biochemistry | Year: 2010

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 first introduce the EC agonists (ligands) and their receptors (CB1 and CB2) and the general actions of EC signaling in various organs and systems. Second, we describe EC signaling in bone and muscle and how dietary PUFA influence the levels of endogenous agonists. 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. ©.

Kim J.,Lipid Chemistry and Molecular Biology Laboratory | Watkins B.A.,Lipid Chemistry and Molecular Biology Laboratory | Watkins B.A.,University of Connecticut Health Center
Journal of Nutritional Biochemistry | Year: 2014

Cyclooxygenase (COX) possesses substrate affinity for the endocannabinoids (EC) anandamide (AEA) and 2-arachidonylglycerol (2-AG). We hypothesized that selective antagonism/activation of the cannabinoid receptors will increase COX activity and the availability of EC as substrates will lead to higher COX activity. Since the relationship between EC signaling of the endocannabinoid system (ECS) and the COX pathway in muscle has not been investigated, we examined agonist, antagonists and polyunsaturated fatty acid effects on ECS genes in myoblasts. At 50% confluency, C2C12 myoblasts were pretreated with 5 μM of the cannabinoid receptor (CB)2 inverse agonist AM630 for 2 h and one with both AM630 and 1 μM of the CB1 antagonist NESS0327. Cell cultures pretreated with AM630 were then administered with 25 μM of either arachidonic acid (20:4n6), eicosapentaenoate (EPA) (20:5n3), docosahexaenoate (DHA) (22:6n3), AEA or bovine serum albumin (vehicle control) for 24 h. Quantitative polymerase chain reaction analyses were performed looking at ECS and prostaglandin genes. Total COX activity and COX-1 protein were greater in the AM630+AEA-treated cells compared to all other cell cultures. The mRNA for the AEA synthesis enzyme N-acyl phosphatidylethanolamine phospholipase D and the 2-AG synthesis enzymes diacylglycerol lipase (DAGL)α and DAGLβ were higher in AM630+EPA-treated cells compared to the other groups. The mRNA levels of CB1 and CB2 were both highest in the AM630+EPA group. The mRNA for interleukin-6 and tumor necrosis factor-α was higher with AEA but lower with DHA and docosahexaenoyl ethanolamide (DHEA), supporting previous findings that the EC AEA supports activation of the COX system. These findings suggest that COX activity and protein levels are influenced by the ECS, specifically by the ligand AEA for CB1 and by inverse agonism of CB2. © 2014.

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