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Title:   Author  item
                                            DUNN, TAMARA - University Of Californiaitem
                                            KEENAN, ALISON - University Of Californiaitem
                                            THOMAS, ANTHONY - University Of Californiaitem
                                            Newman, Johnitem
                                            Adams, Sean
  Submitted to: Nutrition and Metabolism
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 5/6/2014
                                    Publication  Date: 7/3/2014
                                    Citation: Dunn, T.N., Keenan, A.H., Thomas, A.P., Newman, J.W., Adams, S.H. 2014. A diet containing a nonfat dry milk matrix significantly alters systemic endocannabinoids and oxylipins in diet-induced obese mice. Nutrition and Metabolism. 11:1-12.Interpretive Summary: Diets rich in dairy foods have been associated with metabolic health, especially under conditions of high fat feeding that typically promotes obesity and related disorders.  In animal models, dairy-based proteins and matrices reduce body fat, lower inflammation, and prevent steatosis (liver fat accumulation).  The mechanisms that underlie these effects remain to be fully elaborated, but may involve effects on biochemical pathways and metabolism to bring about changes in bioactive lipids (e.g., oxylipins and endocannabinoids) that can impact adipose, neuron and liver tissues.  The current study used a diet-induced obese (DIO) mouse model to evaluate whether a non-fat dry milk and lactose-based diet alters these lipids in blood concurrent to improved metabolic health outcomes.   As reported previously, mice fed NFDM had less body fat and reduced gene expression markers of adipose inflammation than CONTROL mice despite greater cumulative energy intake.  Moreover, NFDM fed mice lipid mediator profiles were distinct from CONTROL and high calcium fed 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).  CONCLUSIONS:  Differences in specific plasma lipid mediator profiles reflect the metabolic and inflammatory phenotypes seen in NFDM feeding.
                                Technical Abstract: BACKGROUND: 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.
METHODS: 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. 
RESULTS:  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).  CONCLUSIONS:  Differences in specific plasma lipid mediator profiles reflect the metabolic and inflammatory phenotypes seen in NFDM feeding.


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