BIOMARKERS OF DE NOVO LIPOGENESIS AND METHODS USING THE SAME
Biomarkers relating to de novo lipogenesis are provided, as well as methods for using such biomarkers in an Index to assess DNL. In addition, methods for diagnosing, determining predisposition to, and monitoring progression/regression of diseases related to DNL are provided. Also provided are methods of monitoring the efficacy of treatments for diseases related to DNL as well as other methods based on biomarkers of DNL.
1 - 45 . (canceled)
46 . A method of estimating de novo lipogenesis in a subject comprising:
measuring the levels of two or more fatty acid biomarkers in a biological sample wherein the two or more fatty acid biomarkers are selected from the group consisting of the total level of myristic acid (14:0), the total level of myristoleic acid (14:1n5), the total level of palmitate (16:0), the total level of palmitoleate (16:1n7), the total level of sapienic acid (16:1n10), the total level of 18:1n10, the total level of squalene, the total level of 6-octadecenoic acid (18:1n12), the total level of linoleate (18:2n6), the total level of arachidonic acid (20:4n6) the total level of docosaheaenoic acid (22:6n3), the level of myristic acid (14:0) in one or more lipid class, the level of myristoleic acid (14:1n5) in one or more lipid class, the level of palmitate (16:0) in one or more lipid class, the level of palmitoleate (16:1n7) in one or more lipid class, the level of sapienic acid (16:1n10) in one or more lipid class, the level of 18:1n10 in one or more lipid class, the level of squalene in one or more lipid class, the level of 18:1n12 in one or more lipid class, the level of linoleate (18:2n6) in one or more lipid class, the level of arachidonic acid (20:4n6) in one or more lipid class, and the level of docosaheaenoic acid (22:6n3) in one or more lipid class in a sample collected from a subject; and
using a statistical model comprised of the measured levels of the two or more fatty acid biomarkers to generate a de novo lipogenesis index to estimate the de novo lipogenesis in the subject.
47 . The method of claim 46 , wherein the fatty acid biomarkers comprise the total levels of palmitate (16:0), palmitoleate (16:1n7) and linoleate (18:2n6) in blood.
48 . The method of 47, wherein the fatty acid biomarkers further comprise the total levels of myristic acid (14:0) and myristoleic acid (14:1n5) in blood.
49 . The method of claim 48 , wherein the fatty acid biomarkers further comprise the total levels of arachidonic acid (20:4n6) and docosaheaenoic acid (22:6n3) in blood.
50 . The method of claim 46 , wherein the biological sample is selected from the group consisting of a sebum sample, a skin sample, an epidermal sample, and a skin cell sample and wherein the two or more biomarkers are selected from the group consisting of 16:0, 16:1n7, 16:1n10, 18:1n10, 18:1n12, 14:0, 14:1n5, 18:2n6, 20:4n6, squalene, and 22:6n3 and combinations thereof.
51 . The method of claim 46 , wherein the fatty acid biomarkers are measured in one or more individual lipid classes selected from the group consisting of triacylglycerides, phosphatidylcholine, and cholesteryl esters.
52 . The method of claim 49 , wherein the fatty acid biomarkers are measured after separating the fatty acids from their backbone.
53 . The method of claim 49 , wherein the fatty acid biomarkers are measured as an intact complex lipid species.
54 . The method of claim 46 , wherein the fatty acid biomarkers are measured in total blood lipids.
55 . The method of claim 46 , wherein the fatty acid biomarkers are expressed as a proportion of total fatty acids.
56 . The method of claim 55 , wherein the proportion is in mole %.
57 . The method of claim 46 , wherein the mathematical model is a linear combination of the measured level of each biomarker in the model whereby positive markers have positive coefficients and negative markers have negative coefficients.
58 . The method of claim 46 , wherein the mathematical model comprises a ratio of a positive marker to a negative marker.
59 . The method of claim 58 , wherein the ratio consists of the sum of positive markers to the sum of negative markers.
60 . The method of claim 46 , wherein the de novo lipogenesis index score is calculated by using one of the following models:
DNL= a (16:0)+ b (16:1 n 7)− c (18:2 n 6); (i)
DNL=( a (16:0)+ b (16:1 n 7))/ c (18:2 n 6); (ii)
DNL= a (16:0)+ b (16:1 n 7)− c (18:2 n 6)+ d (14:0)+ e (14:1 n 5); (iii)
DNL= a (16:0)+ b (16:1 n 7)− c (18:2 n 6)+ d (14:0)+ e (14:1 n 5)− f (20:4 n 6)− g (22:6 n 3); (iv)
DNL= a (16:0)+ b (16:1 n 10)− c (18:2 n 6); or (v)
DNL= a (16:0)+ b (16:1 n 10)− c (squalene), (vi)
wherein a, b, c, d, e, f, g, are constant numbers; wherein (16:0), (16:1n7), 18:2n6), (14:0), (14:1n5), (20:4n6), (22:6n3), (16:1n10) and squalene are measured levels of the two or more biomarkers; and DNL is the predicted de novo lipogenesis score.
61 . The method of claim 46 , wherein the sebum de novo lipogenesis index score is calculated by using one of the following models:
Sebum DNL1 =a (16:0)+ b (16:1 n 10)− c (18:2 n 6), or (i)
Sebum DNL2 =a (16:0)+ b (16:1 n 10)− c (squalene), (ii)
wherein a, b, and c, are constant numbers; wherein (16:0), (16:1n10), (18:2n6) and squalene are measured levels of the two or more biomarkers; and DNL is the predicted sebum de novo lipogenesis score.