0
selected
-
1.
Effects of Intermittent Fasting or Calorie Restriction on Markers of Lipid Metabolism in Human Skeletal Muscle.
Liu, B, Hutchison, AT, Thompson, CH, Lange, K, Wittert, GA, Heilbronn, LK
The Journal of clinical endocrinology and metabolism. 2021;(3):e1389-e1399
Abstract
CONTEXT Impaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR). OBJECTIVE In a secondary analysis of a randomized controlled trial, we compared the effects of intermittent fasting (IF) and CR on markers of lipid metabolism in muscle. DESIGN Seventy-six women (body mass index, 25-40 kg/m2) were randomly assigned to 1 of 3 diets for 8 weeks and provided foods at 70% (CR70 and IF70) or 100% (IF100) of energy requirements. IF groups ate breakfast prior to a 24-hour fast on 3 nonconsecutive days per week. On nonfasting days, IF70 ate at 100% and IF100 ate at 145% of energy requirements to achieve the prescribed target. Weight, body composition, insulin sensitivity by clamp, nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and markers of lipid metabolism and oxidative stress in muscle by quantitative polymerase chain reaction were measured at baseline and week 8 following a 12-hour overnight fast (all groups) and 24-hour fast (IF groups). RESULTS IF70 resulted in greater weight and fat loss and reduced NEFAs vs CR70 and IF100 after an overnight fast. IF70 and IF100 induced a greater reduction only in mRNA levels of antioxidant enzymes glutathione peroxidase 1 (GPX1), superoxide dismutase 1, soluble (SOD1), and SOD2 vs CR70. Fasting for 24 hours increased NEFAs and BHB in IF groups, but impaired insulin sensitivity and increased PLIN5 mRNA levels. CONCLUSIONS In comparison to CR, IF did not increase markers of lipid metabolism in muscle, but reduced expression of antioxidant enzymes. However, fasting-induced insulin resistance was detected, alongside increased PLIN5 expression, potentially reflecting transient lipid storage.
-
2.
Proteomic Analysis of Human Plasma during Intermittent Fasting.
Harney, DJ, Hutchison, AT, Hatchwell, L, Humphrey, SJ, James, DE, Hocking, S, Heilbronn, LK, Larance, M
Journal of proteome research. 2019;(5):2228-2240
Abstract
Intermittent fasting (IF) increases lifespan and decreases metabolic disease phenotypes and cancer risk in model organisms, but the health benefits of IF in humans are less clear. Human plasma derived from clinical trials is one of the most difficult sample sets to analyze using mass spectrometry-based proteomics due to the extensive sample preparation required and the need to process many samples to achieve statistical significance. Here, we describe an optimized and accessible device (Spin96) to accommodate up to 96 StageTips, a widely used sample preparation medium enabling efficient and consistent processing of samples prior to LC-MS/MS. We have applied this device to the analysis of human plasma from a clinical trial of IF. In this longitudinal study employing 8-weeks IF, we identified significant abundance differences induced by the IF intervention, including increased apolipoprotein A4 (APOA4) and decreased apolipoprotein C2 (APOC2) and C3 (APOC3). These changes correlated with a significant decrease in plasma triglycerides after the IF intervention. Given that these proteins have a role in regulating apolipoprotein particle metabolism, we propose that IF had a positive effect on lipid metabolism through modulation of HDL particle size and function. In addition, we applied a novel human protein variant database to detect common protein variants across the participants. We show that consistent detection of clinically relevant peptides derived from both alleles of many proteins is possible, including some that are associated with human metabolic phenotypes. Together, these findings illustrate the power of accessible workflows for proteomics analysis of clinical samples to yield significant biological insight.
-
3.
Use of Hydroxychloroquine Is Associated With Improved Lipid Profile in Rheumatoid Arthritis Patients.
Restrepo, JF, Del Rincon, I, Molina, E, Battafarano, DF, Escalante, A
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases. 2017;(3):144-148
-
-
Free full text
-
Abstract
BACKGROUND/PURPOSE We examined the association between hydroxychloroquine (HCQ) and plasma lipid and glucose levels in rheumatoid arthritis (RA) cohort. METHODS This is a retrospective cohort analysis of 1261 RA patients comparing fasting lipid profiles and plasma glucose between patients who were and were not taking HCQ. We divided patients into 3 groups based on HCQ exposure during follow-up: those who had never taken HCQ, those who took it intermittently, and those who took it continuously. We used multivariable models and propensity scoring to compensate for the effect of nonrandom treatment assignment. RESULTS We followed 1261 RA patients for a total of 4605 observations between 1996 and 2014. After adjusting for age, sex, ethnicity, other disease-modifying antirheumatic drugs (DMARDs), lipid-lowering medications, body mass index (BMI), and smoking, patients taking HCQ at baseline had significantly lower total cholesterol (TC) (P ≤ 0.001), low-density lipoprotein (LDL) (P ≤ 0.001), triglycerides (P = 0.013), and lipid profile ratios TC/high-density lipoprotein (HDL) (P ≤ 0.001) and LDL/HDL (P ≤ 0.001), as well as higher HDL (P ≤ 0.001).In longitudinal analyses, after adjusting for confounders, patients who continuously took HCQ showed significantly lower TC, LDL, TC/HDL, and LDL/HDL and higher HDL (P ≤ 0.01). Fasting plasma glucose levels were not significantly associated with HCQ exposure. CONCLUSIONS Hydroxychloroquine use was associated with lower lipid levels but not with the plasma glucose in this RA cohort. These findings support the need for a randomized trial to establish the role of HCQ in cardiovascular disease prevention in RA patients.
-
4.
Effects of E2 and E2/norgestimate hormone therapy on elevated baseline lipids.
Langer, RD, Friedman, AJ
The Journal of reproductive medicine. 2006;(8):610-6
Abstract
OBJECTIVE To evaluate lipid effects of estradiol/ norgestimate hormone therapy in postmenopausal women with elevated lipid levels. STUDY DESIGN Postmenopausal women were randomized to E2, 1 mg/intermittent norgestimate (NGM) 90 microg (n = 31), or opposed E2, 1 mg (n = 36), in a 12-month trial. A subset analysis was conducted on participants with unfavorable baseline lipid levels, either total cholesterol (TC) levels > 200 mg/dL, high-density lipoprotein cholesterol (HDL-C) levels < 40 mg/dL, low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL or triglyceride levels > or = 150 mg/dL. Mean changes and categorical shifts were assessed on fasting blood samples collected at baseline and at 7 and 12 months. RESULTS Twelve-month mean changes from baseline in women treated with E2/NGM included a 19.8% increase in HDL-C and decreases of 13.4% in LDL-C, 17.5% in triglycerides and 3.3% in TC. Women with poorer lipid profiles at baseline showed the greatest benefit. Results were similar in women randomized to unopposed E2. CONCLUSION E2/NGM and unopposed E2 were similarly beneficial in modifying lipid fractions in women with unfavorable baseline levels.