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Fulltext The effect of exercise in a fasted state on plasma low-density lipoprotein cholesterol concentrations in males and females

Bradshaw L, Koumanov F, Berry S, Betts JA, Gonzalez J

Exp Physiol, 2023 Apr;108(4):543-548.
PMID: 36809567 DOI: 10.1113/EP091005

Cardiovascular disease (CVD) is the leading cause of death worldwide. Physical activity interventions improve almost all modifiable CVD risk factors, but the effect of physical activity on low density lipoprotein cholesterol (LDL-C) is uncertain. This may be due to lack of research on the feeding status in which the physical activity is performed. The aim of this study is to investigate the effect of fasted versus fed exercise on LDL-C concentrations in males and females. One hundred healthy participants, equal males and females, aged between 25 and 60 years will be recruited and will undergo a home-based 12-week exercise intervention. After baseline testing, participants will be randomized to a fasted exercise (exercise after an 8-h fast) or fed exercise (exercise 90-180 min after ingestion of 1 g kg-1 CHO) group and will perform 50 min of moderate intensity exercise (e.g., 95% heart rate of lactate threshold 1) three times a week either before or after a high carbohydrate (1 g kg-1 ) meal. Participants will visit the laboratory again at week 4 and week 12 and measurements will be taken for body composition, resting blood pressure, fasting blood glucose, lipid profiles and systemic inflammation, lactate threshold, and 14-day blood glucose control.
Fulltext Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese

Edinburgh RM, Bradley HE, Abdullah NF, Robinson SL, Chrzanowski-Smith OJ, Walhin JP, et al.

J Clin Endocrinol Metab, 2020 03 01;105(3).
PMID: 31628477 DOI: 10.1210/clinem/dgz104

CONTEXT: Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness.
OBJECTIVE: To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism.
DESIGN: (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study).
SETTING: General community.
PARTICIPANTS: Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study).
INTERVENTIONS: Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion.
RESULTS: Acute Study-exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: -3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (-1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study-postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs -21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05).
CONCLUSIONS: Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.
Fulltext Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

Glubb DM, Maranian MJ, Michailidou K, Pooley KA, Meyer KB, Kar S, et al.

Am J Hum Genet, 2015 Jan 08;96(1):5-20.
PMID: 25529635 DOI: 10.1016/j.ajhg.2014.11.009

Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.

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