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1.
Lipidomic Response to Coffee Consumption.
Kuang, A, Erlund, I, Herder, C, Westerhuis, JA, Tuomilehto, J, Cornelis, MC
Nutrients. 2018;(12)
Abstract
Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry⁻mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p < 0.05 and q < 0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p < 0.05 and q > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.
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2.
Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes.
Ferrannini, E, Baldi, S, Frascerra, S, Astiarraga, B, Heise, T, Bizzotto, R, Mari, A, Pieber, TR, Muscelli, E
Diabetes. 2016;(5):1190-5
Abstract
Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release. In type 2 diabetes (T2D), along with decrements in plasma glucose and insulin levels and increments in glucagon release, sodium-glucose cotransporter 2 (SGLT2) inhibitors induce stimulation of endogenous glucose production (EGP) and a suppression of tissue glucose disposal (TGD). We measured fasting and postmeal glucose fluxes in 25 subjects without diabetes using a double glucose tracer technique; in these subjects and in 66 previously reported patients with T2D, we also estimated lipolysis (from [(2)H5]glycerol turnover rate and circulating free fatty acids, glycerol, and triglycerides), lipid oxidation (LOx; by indirect calorimetry), and ketogenesis (from circulating β-hydroxybutyrate concentrations). In both groups, empagliflozin administration raised EGP, lowered TGD, and stimulated lipolysis, LOx, and ketogenesis. The pattern of glycosuria-induced changes was similar in subjects without diabetes and in those with T2D but quantitatively smaller in the former. With chronic (4 weeks) versus acute (first dose) drug administration, glucose flux responses were attenuated, whereas lipid responses were enhanced; in patients with T2D, fasting β-hydroxybutyrate levels rose from 246 ± 288 to 561 ± 596 µmol/L (P < 0.01). We conclude that by shunting substantial amounts of carbohydrate into urine, SGLT2-mediated glycosuria results in a progressive shift in fuel utilization toward fatty substrates. The associated hormonal milieu (lower insulin-to-glucagon ratio) favors glucose release and ketogenesis.
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3.
Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1 H MRS study.
Qi, J, Fong, Y, Saltz, L, D'Angelica, MI, Kemeny, NE, Gonen, M, Shia, J, Shukla-Dave, A, Jarnagin, WR, Do, RK, et al
NMR in biomedicine. 2013;(2):204-12
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Abstract
Hepatic steatosis is a hallmark of chemotherapy-induced liver injury. We made serial (1) H MRS measurements of hepatic lipids in patients over the time course of a 24-week chemotherapeutic regimen to determine whether (1) H MRS could be used to monitor the progression of chemotherapy-induced steatosis. Thirty-four patients with stage III or IV colorectal cancer receiving 5-fluorouracil, folinic acid and oxaliplatin (n=21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n=13) were studied prospectively. (1) H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A (1) H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat+water (FFW) was calculated to give a measure of hepatic triglycerides (HTGCs). The methodology was histologically validated in 18 patients and the reproducibility was assessed in 16 normal volunteers. Twenty-seven patients completed baseline, 6-week and 24-week (1) H MRS examinations and one was censored. Thirteen of 26 patients (50%) showed an increase in FFW after completion of treatment. Six patients (23%) developed hepatic steatosis and two patients converted from steatosis to nonsteatotic liver. Patients whose 6-week hepatic lipid levels had increased significantly relative to baseline also had a high probability of lipid elevation relative to baseline at the completion of treatment. Serial (1) H MRS is effective for the monitoring of HTGC changes during chemotherapy and for the detection of chemotherapy-associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks.
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4.
Enhanced skeletal muscle lipid oxidative efficiency in insulin-resistant vs insulin-sensitive nondiabetic, nonobese humans.
Galgani, JE, Vasquez, K, Watkins, G, Dupuy, A, Bertrand-Michel, J, Levade, T, Moro, C
The Journal of clinical endocrinology and metabolism. 2013;(4):E646-53
Abstract
CONTEXT Skeletal muscle insulin resistance is proposed to result from impaired skeletal muscle lipid oxidative capacity. However, there is no evidence indicating that muscle lipid oxidative capacity is impaired in healthy otherwise insulin-resistant individuals. OBJECTIVE The objective of the study was to assess muscle lipid oxidative capacity in young, nonobese, glucose-tolerant, insulin-resistant vs insulin-sensitive individuals. DESIGN AND VOLUNTEERS In 13 insulin-sensitive [by Matsuda index (MI) (22.6 ± 0.6 [SE] kg/m(2)); 23 ± 1 years; MI 5.9 ± 0.1] and 13 insulin-resistant (23.2 ± 0.6 kg/m(2); 23 ± 3 years; MI 2.2 ± 0.1) volunteers, skeletal muscle biopsy, blood extraction before and after an oral glucose load, and dual-energy x-ray absorptiometry were performed. MAIN OUTCOME MEASURES Skeletal muscle mitochondrial to nuclear DNA ratio, oxidative phosphorylation protein content, and citrate synthase and β-hydroxyacyl-CoA dehydrogenase activities were assessed. Muscle lipids and palmitate oxidation ((14)CO2 and (14)C-acid soluble metabolites production) at 4 [1-(14)C]palmitate concentrations (45-520 μM) were also measured. RESULTS None of the muscle mitochondrial measures showed differences between groups, except for a higher complex V protein content in insulin-resistant vs insulin-sensitive volunteers (3.5 ± 0.4 vs 2.2 ± 0.4; P = .05). Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Total palmitate oxidation showed a similar concentration-dependent response in both groups (P = .69). However, lipid oxidative efficiency (CO2 to (14)C-acid soluble metabolites ratio) was enhanced in insulin-resistant vs insulin-sensitive individuals, particularly at the highest palmitate concentration (0.24 ± 0.04 vs 0.12 ± 0.02; P = .02). CONCLUSIONS We found no evidence of impaired muscle mitochondrial oxidative capacity in young, nonobese, glucose-tolerant, otherwise insulin-resistant vs insulin-sensitive individuals. Enhanced muscle lipid oxidative efficiency in insulin resistance could be a potential mechanism to prevent further lipotoxicity.
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5.
Increased nocturnal fat oxidation in young healthy men with low birth weight: results from 24-h whole-body respiratory chamber measurements.
Brøns, C, Lilleøre, SK, Jensen, CB, Toubro, S, Vaag, A, Astrup, A
Metabolism: clinical and experimental. 2013;(5):709-16
Abstract
OBJECTIVE Low birth weight (LBW), a marker of disturbed fetal growth, is associated with adiposity and increased risk of type 2 diabetes (T2D). The aim of the study was to investigate whether LBW is associated with changes in 24-h energy expenditure (EE) and/or substrate utilization rates, potentially contributing to the development of adiposity and/or T2D compared to matched control subjects. MATERIALS/METHODS Forty-six young, healthy men were included in the study; 20 with LBW (≤ 10th percentile) and 26 control subjects with normal birth weight (NBW) (50th-90th percentile). The subjects were fed a weight maintenance diet and 24-h energy expenditure (EE), respiratory quotient (RQ), and substrate oxidation were assessed in a respiratory chamber. RESULTS No differences in 24-h EE, RQ or substrate oxidation were observed between LBW and controls. Interestingly, the LBW group exhibited lower nocturnal RQ compared to controls (0.81 ± 0.01 vs. 0.85 ± 0.01 (mean ± SE), P = 0.01), and hence higher nocturnal fat oxidation (2.55 ± 0.13 vs. 2.09 ± 0.12 kJ/min (mean ± SE), P = 0.02). CONCLUSIONS Young LBW men do not exhibit reductions in 24-h EE. However, LBW subjects display increased nocturnal fat oxidation at the expense of reduced glucose oxidation. We speculate that this may be associated with insufficient capability to retain fat in subcutaneous adipose tissue after meals during day time, with an increased rate of nocturnal and morning lipolysis, and potentially with subtle elevations of gluconeogenesis and of fasting glucose levels in the LBW subjects.
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Carbohydrate quality and quantity affect glucose and lipid metabolism during weight regain in healthy men.
Lagerpusch, M, Enderle, J, Eggeling, B, Braun, W, Johannsen, M, Pape, D, Müller, MJ, Bosy-Westphal, A
The Journal of nutrition. 2013;(10):1593-601
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Abstract
In this controlled, parallel-group feeding trial, we examined the impact of carbohydrate (CHO) intake and glycemic index (GI) on glucose and lipid metabolism during refeeding after weight loss. Healthy men (n = 32 total, age: 25.5 ± 3.9 y, BMI: 23.5 ± 2.0 kg/m2) overconsumed diets containing either 50% or 65% CHO for 1 wk (+50% of energy requirements) and then underwent 3 wk of calorie restriction (CR; -50%) followed by 2 wk of overconsuming (refeeding, +50%) the same diet but with either a low or high GI (40 vs.70 during CR, 41 vs.74 during refeeding) so that glycemic load (GL; dietary CHO content x GI) differed between groups during all phases. Glucose profiles were assessed by continuous interstitial glucose monitoring, insulin sensitivity (IS) by fasting blood sampling, oral glucose tolerance test (OGTT) and hyperinsulinemic-euglycemic clamp, and liver fat by MRI. Daytime area under the curve-glucose during refeeding was higher with high compared with low GI (P = 0.01) and 65% compared with 50% CHO intake (P = 0.05) and correlated with dietary GL (r = 0.71; P < 0.001). IS increased with CR and decreased again with refeeding in all groups. The decrease in OGTT-derived IS was greater with high- than with low-GI diets (-41 vs. -15%; P-interaction = 0.01) and correlated with dietary GL during refeeding (r = -0.51; P < 0.01). Serum triglycerides (TGs) and liver fat also improved with CR (-17 ± 38 mg/dL and -1.1 ± 1.3%; P < 0.05 and <0.001) and increased again with refeeding (+48 ± 48 mg/dL and +2.2 ± 1.6%; P < 0.001). After refeeding, serum TGs and liver fat were elevated above baseline values with 65% CHO intake only (+59.9 ± 37.5 mg/dL and +1.1 ± 1.7%, P-interaction <0.001 and <0.05). In conclusion, a diet low in GI and moderate in CHO content (i.e., low GL) may have health benefits by positively affecting daylong glycemia, IS, and liver fat.
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[Evaluation of the intake of a low daily amount of soybeans in oxidative stress, lipid and inflammatory profile, and insulin resistance in patients with metabolic syndrome].
Bahls, LD, Venturini, D, Scripes, Nde A, Lozovoy, MA, Simão, TN, Simão, AN, Dichi, I, Morimoto, HK
Arquivos brasileiros de endocrinologia e metabologia. 2011;(6):399-405
Abstract
OBJECTIVE Studies show that regular consumption of soybeans reduces the risk of diabetes and cardiovascular diseases. However, most of these studies recommend daily intake of 25 g or more of soy protein, an amount considered high and not well tolerated by patients. The objective of this study was to assess the effect of low daily intake of soybeans in oxidative stress and in components of the metabolic syndrome (MS). SUBJECTS AND METHODS Forty individuals with MS were selected and divided into two groups: control group (n = 20) and soybean-treated group (n = 20), which consumed 12.95 g of soy protein for 90 days. RESULTS After the treatment, the soybean-treated group showed a decrease in fasting glucose and increase in serum HDL and adiponectin. CONCLUSION Low intake of soy protein for 90 days, besides being well tolerated by the patients, was able to improve several parameters related to the pathophysiology of MS.
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Effects of exercise intensity and altered substrate availability on cardiovascular and metabolic responses to exercise after oral carnitine supplementation in athletes.
Broad, EM, Maughan, RJ, Galloway S, DR
International journal of sport nutrition and exercise metabolism. 2011;(5):385-97
Abstract
The effects of 15 d of supplementation with L-carnitine L-tartrate (LC) on metabolic responses to graded-intensity exercise under conditions of altered substrate availability were examined. Fifteen endurance-trained male athletes undertook exercise trials after a 2-d high-carbohydrate diet (60% CHO, 25% fat) at baseline (D0), on Day 14 (D14), and after a single day of high fat intake (15% CHO, 70% fat) on Day 15 (D15) in a double-blind, placebo-controlled, pair-matched design. Treatment consisted of 3 g LC (2 g L-carnitine/d; n = 8) or placebo (P, n = 7) for 15 d. Exercise trials consisted of 80 min of continuous cycling comprising 20-min periods at each of 20%, 40%, 60%, and 80% VO2peak. There was no significant difference between whole-body rates of CHO and fat oxidation at any workload between D0 and D14 trials for either the P or LC group. Both groups displayed increased fat and reduced carbohydrate oxidation between the D14 and D15 trials (p < .05). During the D15 trial, heart rate (p < .05 for 20%, 40%, and 60% workloads) and blood glucose concentration (p < .05 for 40% and 60% workloads) were lower during exercise in the LC group than in P. These responses suggest that LC may induce subtle changes in substrate handling in metabolically active tissues when fatty-acid availability is increased, but it does not affect whole-body substrate utilization during short-duration exercise at the intensities studied.
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Comparative results of a 4-year study on cardiovascular parameters, lipid metabolism, body composition and bone mass between untreated and treated adult growth hormone deficient patients.
Fideleff, HL, Boquete, HR, Stalldecker, G, Giaccio, AV, Sobrado, PG
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2008;(4):318-24
Abstract
OBJECTIVE To evaluate the long-term evolution of cardiovascular parameters, lipid metabolism, body composition and bone mass in untreated and treated adult growth hormone deficient patients (AGHD) comparing the differences between the two groups and within each group. DESIGN Seventy-one AGHD-patients were enrolled; 48 received growth hormone (GH) therapy: treated group (TG) and 23 received no GH therapy: control group (CG). In the TG, 22 were childhood-onset (CO) GH-deficient patients, 18-44 years (12 males) and 26 were adult-onset (AO) GH-deficient patients, 27-66 years (10 males). In the CG, 10 patients were AGHD-CO, 20-43 years (8 males) and 13 were AGHD-AO, 25-70 years (8 males). For patients in the TG, GH was administered at a starting dose of 0.1mg/day, adjusted to maintain IGF-I levels between 0 and 2 SDS for gender and age. At baseline and during the 4th year of replacement therapy or follow-up, the following parameters were evaluated: body mass index, waist circumference, blood glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, total cholesterol/HDL-cholesterol ratio, systolic and diastolic blood pressure, 2-D echocardiogram with mitral Doppler, bone mineral density (total body, lumbar spine, and femoral neck), bone mineral content (BMC) and body composition. RESULTS In the TG, there was a decrease in diastolic blood pressure (-4.0+/-1.8 mmHg, p<0.035) and an increase in blood glucose levels (0.58+/-0.19 mmol/L, p<0.025), bone mineral content (0.2+/-0.0 kg, p<0.015) and bone mineral density of lumbar spine (0.3+/-0.1 SDS, p<0.015) and femoral neck (0.4+/-0.1 SDS, p<0.001). All other variables did not show significant changes in any of the two groups. At year 4, changes (delta) differed between patients in the TG and those in the CG with regard to cholesterol levels (TG: -0.27+/-0.16 mmol/L, CG: 0.34+/-0.23 mmol/L, p<0.045), blood glucose (TG: 0.58+/-0.19 mmol/L, CG: -0.12+/-0.19 mmol/L, p<0.025) and BMC (TG: 0.2+/-0.0 g, CG: 0.0+/-0.0 g, p<0.015). An assessment of the changes in variables over time, with and without therapy, considering CO and AO separately, revealed a significant difference in total cholesterol levels during year 4 in CO patients CO (TG: -0.28+/-0.25 mmol/L and CG: 0.84+/-0.25 mmol/L, p<0.015). No differences related to the time of onset of GHD were found in changes in the remaining variables studied. There were no differences related to gender, GHD etiology or the presence of other pituitary hormone deficiencies in the evolution of the parameters analyzed. CONCLUSIONS Our 4-year study in GH deficient adults showed significant beneficial effects on some cardiovascular risk parameters and BMC in treated patients. However, there are still unsettled issues regarding long-term benefits and these patients should be carefully monitored.
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The effects of liposuction removal of subcutaneous abdominal fat on lipid metabolism are independent of insulin sensitivity in normal-overweight individuals.
Ybarra, J, Blanco-Vaca, F, Fernández, S, Castellví, A, Bonet, R, Palomer, X, Ordóñez-Llanos, J, Trius, A, Vila-Rovira, R, Pérez, A
Obesity surgery. 2008;(4):408-14
Abstract
BACKGROUND Abdominal fat (both visceral and subcutaneous) accumulation is associated with an increased risk of developing insulin resistance. The latter stands as the basis upon which diabetes, hypertension, and atherogenic dyslipidemia tend to build up. Hence, abdominal liposuction (AL) could theoretically hold metabolic benefits. We undertook the present study to assess the effects of AL on carbohydrate and lipid metabolism. METHODS This is a prospective study including 20 healthy volunteers (M2/F18) aged 39.6 +/- 7.7 years old (24-52), body mass index (BMI) = 25.3 +/- 4.7 kg/m(2) (19.8-36) who underwent AL. Before and 4 months after AL, we measured glucose and insulin concentrations, HOMA index [glucose (mM) x IRI (microUI/l)/22.5], free fatty acids (FFA), glycerol, total cholesterol and triglycerides, high-density lipoprotein (HDL)-cholesterol (HDL-c), low-density lipoprotein (LDL)-cholesterol (LDL-c), very low-density lipoprotein (VLDL)-cholesterol (VLDL-c) and apolipoproteins (apo) B, AI and AII, adiponectin (Adp), and ultra-sensitive C-reactive protein (CRP). RESULTS Lipo-aspirate averaged 5.494 +/- 5.297 cc (600-19.000). Weight, BMI, and waist circumference decreased significantly 4 months after surgery by 4.6, 4.6 and 5.9%, respectively. There were significant decrements in FFA (-35%, p < 0.0001), glycerol (-63%, p < 0.0005), VLDL-c (-15.2%; p < 0.001), and triglycerides (-21.3%, p < 0.002), an increase in HDL-c (+10%, p < 0.03), Apo AI (+10.1%, p < 0.02), and Apo AII (+11.8%, p < 0.001). Total cholesterol, LDL-c, ApoB, and the LDL-c/ApoB ratio raised by +15% (p < 0.0005), +27.3% (p < 0.000), +15.1% (p < 0.008) and +2.76% (p < 0.008), respectively. Glucose, insulin, the HOMA index, Adp, and CRP were not significantly altered after AL. CONCLUSION AL in healthy normal weight or slightly overweight subjects improves the major lipoprotein components of obesity-associated dyslipidemia. This improvement occurs independent of insulin sensitivity.