The purpose of this study was to test whether transient increases in homocysteine would promote changes in markers of endothelial injury, cellular fibronectin (cFN), and soluble vascular cell ...adhesion molecule 1 (sVCAM-1). Homocysteine, cFN, and sVCAM-1 concentrations increased significantly in response to a methionine load by 6 hours in human subjects. However, no correlation was observed between homocysteine and cFN or sVCAM-1. To directly test whether homocysteine can injure endothelial cells, human umbilical vein endothelial cells (HUVEC) were incubated with increasing concentrations of homocysteine, plasma, or serum from hyperhomocysteinemic mice or from the methionine-loaded test subjects. cFN release was increased from endothelial cells cultured with plasma (but not serum) of hyperhomocysteinemic transgenic mice or from methionine-loaded human subjects. These data suggest that very high homocysteine concentrations can promote endothelial injury; however, this effect is likely mediated by secondary effects that include a factor(s) present in plasma that affects endothelial cells. Copyright 2003 Elsevier, Inc. All rights reserved.
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Type 2 diabetes (T2D) and the metabolic syndrome (MetS) are more prevalent in Hispanics (H) than nonHispanic whites (NHW) in the US, suggesting that H may be less responsive to the same ...lifestyle intervention as NHW. We therefore compared the effects of a short term exercise and low saturated fat, low sugar diet intervention on T2D and MetS risk factors in H and NHW sedentary adults. Participants (20 NHW: 11F, 9M, age=23.0 y, BMI=25.5; 17 H: 13F, 4M, age=22.7, BMI=25.4) consumed their habitual diets and remained sedentary for 7 days, after which an intravenous glucose tolerance test (IVGTT) was performed. Subjects then completed a 7 day diet/exercise intervention (6 sessions, 40 min/session at 65% VO2 max) followed by a second IVGTT ~16 h later. Pre intervention insulin sensitivity (Si) was lower in H, improved proportionately with the lifestyle intervention, but remained lower than NHW following the intervention (IAUC µU*min/L pre, post: H = 2298, 1635; NHW = 1795, 1211). Despite lower Si, pre test lipids were no different in H compared to NHW, but improved in both groups (total cholesterol mg/dl: H: pre = 150, post = 135, NHW = 162, 147; LDL‐C mg/dl: H = 102, 97; NHW = 107, 95; Small dense LDL particles nmol/L: H: = 423, 393; NHW = 408, 349). These data suggest that despite higher risk for T2D and MetS, young H adults are as metabolically responsive as NHW to a short term diet/exercise intervention.
Funding: CO Ag Expt Station (CLM, MSH)
Grant Funding Source
Colorado Agriculture Experiment Station
Background It has been hypothesized that obese and reduced-obese individuals have decreased oxidative capacity, which contributes to weight gain and regain. Recent data have challenged this concept. ...Objective To determine (1) whether total and dietary fat oxidation are decreased in obese and reduced-obese adults compared to lean but increase in response to an acute exercise bout and (2) whether regular physical activity attenuates these metabolic alterations. Design We measured 24-hr total (whole-room calorimetry) and dietary fat (14C-oleate) oxidation in Sedentary Lean (BM delta = 21.5 plus or minus 1.6; n = 10), Sedentary Obese (BM delta = 33.6 plus or minus 2.5; n = 9), Sedentary Reduced-Obese (RED-SED; BM delta = 26.9 plus or minus 3.7; n = 7) and in Physically Active Reduced-Obese (RED-EX; BM delta = 27.3 plus or minus 2.8; n = 12) men and women with or without an acute exercise bout where energy expended during exercise was not replaced. Results Although Red-SED and Red-EX had a similar level of fatness, aerobic capacity and metabolic profiles were better in Red-EX only compared to Obese subjects. No significant between-group differences were seen in 24-hr respiratory quotient (RQ, Lean: 0.831 plus or minus 0.044, Obese: 0.852 plus or minus 0.023, Red-SED: 0.864 plus or minus 0.037, Red-EX: 0.842 plus or minus 0.039), total and dietary fat oxidation. A single bout of exercise increased total (+27.8%, p<0.0001) and dietary (+6.6%, p = 0.048) fat oxidation across groups. Although exercise did not impact RQ during the day, it decreased RQ during sleep (p = 0.01) in all groups. Red-EX oxidized more fat overnight than Red-SED subjects under both resting (p = 0.036) and negative energy balance (p = 0.003) conditions, even after adjustment for fat-free mass. Conclusion Obese and reduced-obese individuals oxidize as much fat as lean both under eucaloric and negative energy balance conditions, which does not support the hypothesis of reduced oxidative capacity in these groups. Reduced-obese individuals who exercise regularly have markers of metabolic health similar to those seen in lean adults. Both the acute and chronic effects of exercise were primarily observed at night suggesting an important role of sleep in the regulation of lipid metabolism.
Our objective was to determine the clinical services offered by American Board of Obesity Medicine (ABOM) Diplomates and whether guideline concordant services varied by clinical practice attributes. ...We conducted a cross-sectional analysis of the 2019 ABOM Diplomate survey (response rate 19.2%). Respondents (n = 494) self-reported services offered: nutrition, exercise, mental health, minimally invasive bariatric procedures, perioperative bariatric surgical care and FDA-approved anti-obesity medications. We graded concordance of services offered with three evidence-based obesity guidelines, and then conducted bivariate analyses comparing concordance by practice attributes. Most responding ABOM Diplomates offered nutrition (90.1%), exercise (67.8%) and mental health (76.7%). Few offered minimally invasive procedures (24.3%), and most provided perioperative surgical care (63.0%). Most (83.4%) prescribed FDA-approved medications-typically both short- and long-term agents (70.9%). Few Diplomates had low concordance with the American Heart Association/American College of Cardiology/The Obesity Society (AHA/ACC/TOS) guidelines (24.7%). Those who managed more obesity-related conditions and endorsed AHA/ACC/TOS guideline use had higher concordance with these recommendations. No differences in guideline concordance existed by population, clinical effort or location. We found similar findings regarding concordance with ) American Association of Clinical Endocrinologists/American College of Endocrinology and Obesity Medicine Association guidelines. In conclusion, most responding ABOM Diplomates offer evidence-based obesity medicine services. Clinicians may therefore have increased confidence in patient receipt of evidence-based care when referring to an ABOM Diplomate.
Type 2 diabetes (T2D) and the metabolic syndrome (MetS) are prevalent in Hispanics than in the US. It is possible that HIS may be less responsive to a lifestyle intervention aimed at reducing risk ...for T2D and MetS compared to NHW. We evaluated the effects of a short term exercise and low saturated fat, low sugar diet intervention on T2D and MetS risk factors in Mexican American (MA) compared to NHW adults. We performed skeletal muscle biopsies and used a proteomics analysis to determine if differences in expression proteins existed. Participants spent a baseline period of 7 days consuming their normal diets and not participating in any exercise. Subjects then underwent an intravenous glucose tolerance test (IVGTT) and muscle biopsy. Subjects then completed a 7 day diet and exercise intervention. Subjects exercised on a stationary cycle (6 sessions, 40–45 min/session at 65% VO2 max) and consumed food that was provided (low in saturated fat and refined carbohydrates). This 7 day period was followed by a second IVGTT and biopsy ∼17 h following the final exercise bout. Thirty-seven participants (20 NHW: 11F, 9M, age = 23.0 y, BMI = 25.5; 17 MA: 13F, 4M, age = 22.7, BMI = 25.4) completed the study. Pre intervention insulin sensitivity (Si) was lower in MA, improved proportionately with the intervention, but remained lower than NHW following the intervention (IAUC µU*min/L pre, post: MA = 2298, 1635; NHW = 1795, 1211). Despite lower Si, pre and post test lipids were no different in MA compared to NHW, but improved in both groups (total cholesterol: −10%; LDL-C: −10%; TG: −37%; Small dense LDL particles: −13%). Two proteins were differentially expressed: Carnitine palmitoyltransferase 1A (CPT-1) and mitochondrial ATP synthase F1 beta subunit. CPT-1 was 1.7-fold higher in NHW (NHW = 190.4 ± 1.3 vs MA = 109.3 ± 12.6). ATP synthase was 3-fold higher in NHW (NHW= 188.4 ± 10.2 and MA = 62.7 ± 28.4). MA adults are as responsive as NHW to a diet-exercise intervention, however the disparity in insulin sensitivity remains. Differences in risk for T2D and MetS may be related to expression of the mitochondrial proteins, CPT-1 and ATP synthase.
How many steps/day are enough? For adults Tudor-Locke, Catrine; Craig, Cora L; Brown, Wendy J ...
The international journal of behavioral nutrition and physical activity,
07/2011, Volume:
8, Issue:
1
Journal Article
Peer reviewed
Open access
Physical activity guidelines from around the world are typically expressed in terms of frequency, duration, and intensity parameters. Objective monitoring using pedometers and accelerometers offers a ...new opportunity to measure and communicate physical activity in terms of steps/day. Various step-based versions or translations of physical activity guidelines are emerging, reflecting public interest in such guidance. However, there appears to be a wide discrepancy in the exact values that are being communicated. It makes sense that step-based recommendations should be harmonious with existing evidence-based public health guidelines that recognize that "some physical activity is better than none" while maintaining a focus on time spent in moderate-to-vigorous physical activity (MVPA). Thus, the purpose of this review was to update our existing knowledge of "How many steps/day are enough?", and to inform step-based recommendations consistent with current physical activity guidelines. Normative data indicate that healthy adults typically take between 4,000 and 18,000 steps/day, and that 10,000 steps/day is reasonable for this population, although there are notable "low active populations." Interventions demonstrate incremental increases on the order of 2,000-2,500 steps/day. The results of seven different controlled studies demonstrate that there is a strong relationship between cadence and intensity. Further, despite some inter-individual variation, 100 steps/minute represents a reasonable floor value indicative of moderate intensity walking. Multiplying this cadence by 30 minutes (i.e., typical of a daily recommendation) produces a minimum of 3,000 steps that is best used as a heuristic (i.e., guiding) value, but these steps must be taken over and above habitual activity levels to be a true expression of free-living steps/day that also includes recommendations for minimal amounts of time in MVPA. Computed steps/day translations of time in MVPA that also include estimates of habitual activity levels equate to 7,100 to 11,000 steps/day. A direct estimate of minimal amounts of MVPA accumulated in the course of objectively monitored free-living behaviour is 7,000-8,000 steps/day. A scale that spans a wide range of incremental increases in steps/day and is congruent with public health recognition that "some physical activity is better than none," yet still incorporates step-based translations of recommended amounts of time in MVPA may be useful in research and practice. The full range of users (researchers to practitioners to the general public) of objective monitoring instruments that provide step-based outputs require good reference data and evidence-based recommendations to be able to design effective health messages congruent with public health physical activity guidelines, guide behaviour change, and ultimately measure, track, and interpret steps/day.
Cisplatin resistance in head and neck squamous cell carcinoma (HNSCC) reduces survival. In this study we hypothesized that methylation of key genes mediates cisplatin resistance. We determined ...whether a demethylating drug, decitabine, could augment the anti-proliferative and apoptotic effects of cisplatin on SCC-25/CP, a cisplatin-resistant tongue SCC cell line. We showed that decitabine treatment restored cisplatin sensitivity in SCC-25/CP and significantly reduced the cisplatin dose required to induce apoptosis. We then created a xenograft model with SCC-25/CP and determined that decitabine and cisplatin combination treatment resulted in significantly reduced tumor growth and mechanical allodynia compared to control. To establish a gene classifier we quantified methylation in cancer tissue of cisplatin-sensitive and cisplatin-resistant HNSCC patients. Cisplatin-sensitive and cisplatin-resistant patient tumors had distinct methylation profiles. When we quantified methylation and expression of genes in the classifier in HNSCC cells in vitro, we showed that decitabine treatment of cisplatin-resistant HNSCC cells reversed methylation and gene expression toward a cisplatin-sensitive profile. The study provides direct evidence that decitabine restores cisplatin sensitivity in in vitro and in vivo models of HNSCC. Combination treatment of cisplatin and decitabine significantly reduces HNSCC growth and HNSCC pain. Furthermore, gene methylation could be used as a biomarker of cisplatin-resistance.
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