Author
BORKOWSKI, KAMIL - University Of California, Davis | |
YIM, SUN - University Of California, Davis | |
HOLT, ROBERTA - University Of California, Davis | |
HACKMAN, ROBERT - University Of California, Davis | |
KEEN, CARL - University Of California, Davis | |
Newman, John | |
SHEARER, GREGORY - Pennsylvania State University |
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/11/2019 Publication Date: 3/11/2019 Citation: Borkowski, K., Yim, S.J., Holt, R.R., Hackman, R.M., Keen, C.L., Newman, J.W., Shearer, G.C. 2019. Walnuts change lipoprotein composition suppressing TNFa-stimulated cytokine production by diabetic adipocyte. Journal of Nutritional Biochemistry. 68:51-58. https://doi.org/10.1016/j.jnutbio.2019.03.004. DOI: https://doi.org/10.1016/j.jnutbio.2019.03.004 Interpretive Summary: Consuming walnuts has been associated with health benefits. This study investigated the impact of consuming a modest amount of walnuts for a short period of time on the concentrations and relative abundance of fatty acids and a suite of their bioactive metabolites within transport vesicles in blood plasma, call lipoprotein particles. We then evaluated the impact of the structural changes in the low density lipoprotein particle (LDL) on the inflammatory response of cultured adipose cells. Hypercholesterolemic, postmenopausal females were selected from groups randomized to 4wks of 5 g/d (i.e. 0.2 servings/d; n=5) or 40 g/d (i.e. 1.6 servings/d; n=15) of walnuts. Esterified and non-esterified fatty acids and their oxygenated metabolites were quantified in isolated lipoproteins. Diabetic and non-diabetic primary adipocytes were exposed to LDL (n=10), and the production of cytokines were measured with and without cellular stimulation with the inflammatory cytokine tumor necrosis factor alpha (TNFa). As unique effects were observed at the lower walnut dose, the study was prospectively analyzed with a change from baseline approach. The higher walnut dose elevated alpha-linolenic acid and its epoxides in all lipoproteins, enriched high density lipoprotein (HDL) long chain fatty acid epoxides, and depleted very low density lipoprotein (VLDL) and LDL, but not HDL mid-chain alcohols. The higher dose LDL also reduced TNFa-induced diabetic adipocyte production of interleukin-6 (-39% p=0.0006) and interleukin-8 (-25% p=0.01), changes inversely correlated with levels of alpha-linolenic acid-derived epoxides but not alpha-linolenic acid itself. In conclusion, modest walnut consumption can alter lipoprotein Technical Abstract: Walnut consumption can provide vascular and metabolic health benefits. This study investigated the impact of walnut consumption on lipoprotein particle lipid composition and the resulting anti-inflammatory behavior of LDL particles. Hypercholesterolemic, postmenopausal females were randomized to 4wks of 5 g/d (i.e. 0.2 servings/d; n=5) or 40 g/d (i.e. 1.6 servings/d; n=15) of walnuts. Esterified and non-esterified lipids and oxylipins were quantified in isolated lipoproteins. Diabetic and non-diabetic primary adipocytes were exposed to LDL (n=10), and TNFa-stimulated adipokine production was measured. As unique effects were observed at the low dose the study was prospectively analyzed with a change from baseline approach. The higher walnut dose elevated alpha-linolenic acid and its epoxides in all lipoproteins, enriched HDL long chain fatty acid epoxides, and depleted VLDL and LDL, but not HDL mid-chain alcohols. The higher dose LDL also reduced TNFa-induced diabetic adipocyte production of IL-6 (-39% p=0.0006) and IL-8 (-25% p=0.01), changes inversely correlated with levels of alpha-linolenic acid-derived epoxides but not alpha-linolenic acid itself. In conclusion, modest walnut consumption can alter lipoprotein lipid profiles and enhance their ability to inhibit TNFa-dependent pro-inflammatory responses in diabetic primary adipocytes. Walnut associated health benefits may be linked in part to changes in lipoprotein payload and function. |