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A diet containing a nonfat dry milk matrix significantly alters systemic oxylipins and the endocannabinoid 2-arachidonoylglycerol (2-AG) in diet-induced obese mice

Tamara N Dunn15, Alison H Keenan125, Anthony P Thomas135, John W Newman1456* and Sean H Adams1456*

Author Affiliations

1 Graduate Group in Nutritional Biology, University of California, Davis, USA

2 Current address: Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA

3 Current Address: Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA

4 Obesity & Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA, USA

5 Department of Nutrition, University of California, Davis, USA

6 USDA-ARS Western Human Nutrition Research Center, 430 W. Health Sciences Dr, Davis, CA 95616, USA

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Nutrition & Metabolism 2014, 11:24  doi:10.1186/1743-7075-11-24

Published: 30 May 2014



Diets rich in dairy and/or calcium (Ca) have been associated with reductions in adiposity and inflammation, but the mechanisms underlying this remain to be fully elucidated. Oxylipins and endocannabinoids are bioactive lipids, which influence energy homeostasis, adipose function, insulin signaling, and inflammation. Our objective was to determine if these metabolites associate with metabolic and inflammatory phenotypes stemming from dietary Ca and dairy in diet induced obese mice.


In one study, C57BL6/J mice were fed high fat diets (45% energy) with varying dietary matrices for 12 weeks: soy protein and Ca adequate (0.5%; CONTROL), soy protein and high Ca (1.5%; HighCa), or nonfat-dry-milk based high Ca (NFDM). In a second study, mice were pre-fattened for 12 weeks on the CONTROL high fat diet, and then fed one of three high fat diets for an additional 8 weeks: CONTROL, HighCa, or NFDM. In both studies, adiposity and associated metabolic and inflammatory outcomes were measured and a targeted lipidomics analysis was performed on plasma collected during the post-absorptive condition.


As reported previously, mice fed NFDM had less body fat and reduced mRNA markers of adipose inflammation (p < 0.05) than CONTROL mice despite greater cumulative energy intake. Moreover, NFDM fed mice lipid mediator profiles were distinct from CONTROL and HighCa mice. NFDM fed mice showed elevated plasma monoacylglycerols (6 – 46% increase from CONTROL), including 2-arachidonoylglycerol (2-AG), and reduced fatty acid diols (8-75% decrease from CONTROL).


Differences in specific plasma lipid mediator profiles reflect the metabolic and inflammatory phenotypes seen in NFDM feeding.