Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids.

Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5-25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30-40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.

Effectiveness of vitamin D therapy in improving metabolomic biomarkers in obesity phenotypes: Two randomized clinical trials.

BACKGROUND: Uncertainty remains about the effect of vitamin D therapy on biomarkers of health status in obesity. The molecular basis underlying this controversy is largely unknown. OBJECTIVE: To address the existing gap, our study sought to compare changes in metabolomic profiles of obesity phenotypes (metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO)) patients with sub-optimal levels of vitamin D following vitamin D supplementation. METHODS: We conducted two randomized double-blind clinical trials on participants with either of the two obesity phenotypes from Tehran province. These phenotypes were determined by the Adult Treatment Panel-III criteria. Patients in each of the MHO (n = 110) and MUHO (n = 105) groups were separately assigned to receive either vitamin D (4000 IU/d) or placebo for 4 months. Pre- and post-supplementation plasma metabolomic profiling were performed using Liquid chromatography coupled to a triple quadrupole mass spectrometry. Multivariable linear regression was used to explore the association of change in each metabolite with the trial assignment (vitamin D/placebo) across obesity phenotypes. RESULTS: Metabolites (n = 104) were profiled in 82 MHO and 78 MUHO patients. After correction for multiple comparisons, acyl-lysophosphatidylcholines C16:0, C18:0, and C18:1, diacyl-phosphatidylcholines C32:0, C34:1, C38:3, and C38:4, and sphingomyelin C40:4 changed significantly in response to vitamin D supplementation only in MUHO phenotype. The interaction analysis revealed that vitamin D therapy was different between the two obesity phenotypes based on acyl-lysophosphatidylcholines C16:0 and C16:1 and citrulline which were altered significantly after supplementation. Changes in metabolites were associated with changes in cardiometabolic biomarkers after the intervention. CONCLUSIONS: Vitamin D treatment influenced the obesity-related plasma metabolites only in adults with obesity and metabolically unhealthy phenotype. Therefore, not all patients with obesity may benefit from an identical strategy for vitamin D therapy. These findings provide mechanistic basis highlighting the potential of precision medicine to mitigate diseases in health-care settings.

Effects of two-months balanced diet in metabolically healthy obesity: lipid correlations with gender and BMI-related differences.

BACKGROUND: Nowadays no researches has been performed on fatty acid profile (FA) and desaturase activity in metabolically healthy obesity (MHO). The aim of this study was to assessed gender and BMI-related difference in FA, estimated desaturase activities and the efficacy on metabolic changes produced by 2-months well-balance diet in MHO subjects. METHODS: In 103 MHO subjects (30/73 M/F; age:42.2 ± 9.5) FA, estimated desaturase activity, body composition (by DXA), Body Mass Index (BMI), lipid profile, adipokines (leptin, adiponectin, grelin, glucagon-like peptide-1), insulin resistence (by Homestasis metabolic assessment), C-reactive proteine, Atherogenic index of plasma (AIP) and Body Shape Index (ABSI) have been assessed. Gender and BMI related difference have been evaluated and the efficacy produced by 2-months well-balance diet has been considered. RESULTS: At baseline, obese subjects, compared to overweight, show a significantly higher oleic (p <0.050), monounsaturated fatty acids (p <0.040), C18:0 delta-9 desaturase activity (D9D) (p <0.040) and lower linoleic acid (p <0.020), polyunsaturated fatty acids (p <0.020) and n-6 LCPUFA (p <0.010). Concerning gender-related difference, women show a significantly higher arachidonic acid (p <0.001), polyunsaturated fatty acids (p <0.001), n-6 LCPUFA (p <0.002), and lower monounsaturated fatty acids (p <0.001), D6D activity (p <0.030), C18:0 D9D (0.000) and C16:0 D9D (p <0.030). The 2-months diet was associated with a significantly increase in arachidonic acid (p = 0.007), eicosapentaenoic acid (p = 0.030), docosahexaenoic acid (p <0.001), long chain omega 3 polyunsaturated fatty acids (n-3 LCPUFA) (p <0.001), delta-5 desaturase activity (D5D) (p = 0.002), glucagon like peptide-1 (p <0.001) and a significant decrease in palmitoleic acid (p = <0.030), n-6/n-3 LCPUFA (p <0.001), insulin resistance (p = 0.006), leptin (p = 0.006), adiponectin (p <0.001), grelin (p = 0.030), CRP (p = 0.004), BMI (p <0.001) and android fat mass (p <0.001). CONCLUSIONS: The balanced diet intervention was effective in improving metabolic indices.