Evidence for an abnormal postprandial response to a high-fat meal in women predisposed to obesity

1994 ◽  
Vol 267 (4) ◽  
pp. E549-E559 ◽  
Author(s):  
A. Raben ◽  
H. B. Andersen ◽  
N. J. Christensen ◽  
J. Madsen ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Weight Maintenance ◽  
Plasma Concentrations ◽  
Gastric Inhibitory Polypeptide ◽  
Normal Weight ◽  
High Fat ◽  
Pronounced Increase ◽  
Nonesterified Fatty Acids ◽  
Adipose Tissue Lipoprotein Lipase ◽  
History Of Obesity ◽  
Fat Meal

The present study was undertaken to investigate fat metabolism after a high-fat meal [50 energy percent (E%) fat] in formerly obese subjects with a familial history of obesity. Twelve normal-weight postobese women (PO) and 12 closely matched controls were given the test meal after a 2-day carbohydrate-rich weight-maintenance diet (58 E% carbohydrate). Whereas the thermic effect of the meals was similar in the two groups, postprandial fat oxidation was 2.5 times more suppressed in PO compared with controls (P < 0.05). A similarly enhanced suppression of arterialized plasma concentrations of nonesterified fatty acids was seen postprandially in PO (P < 0.05), possibly due to a more marked suppression of epinephrine and a reduced glucagon response in PO than in controls. Moreover, the postprandial plasma triglyceride response was attenuated and only amounted to 43% of that in controls (P < 0.05). This may be explained by a more pronounced increase in gastric inhibitory polypeptide in PO, giving rise to a higher adipose tissue lipoprotein lipase activity. No other differences were found in plasma substrates and hormones or in subjective appetite scores. In conclusion, a metabolic and hormonal pattern favoring lipid storage was observed in postobese subjects after a high-fat meal.

scholarly journals Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Calcitonin Gene-Related Peptide (CGRP)-I and Procalcitonin (Pro-CT) Production in Human Adipocytes

2011 ◽  
Vol 96 (2) ◽  
pp. E297-E303 ◽  
Author(s):  
Katharina Timper ◽  
Jean Grisouard ◽  
Tanja Radimerski ◽  
Kaethi Dembinski ◽  
Ralph Peterli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Obese Patients ◽  
Human Adipocytes ◽  
High Fat ◽  
Metabolic Complications ◽  
Related Peptide ◽  
Fat Meal

abstract Context: Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet. Objective: The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients. Design and Participants: Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed. Results: Treatment with 1 nm GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P &lt; 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P &lt; 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P &lt; 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P &lt; 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P &lt; 0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients. Conclusion: GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations.

Dasatinib Can Be Administered Orally with or without a Meal.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4569-4569 ◽  
Author(s):  
Sanjeev Kaul ◽  
Chiyuan Wu ◽  
Shelley Mayfield ◽  
James Manning ◽  
Anne Blackwood-Chirchir
Keyword(s):  
Adverse Events ◽  
Healthy Adult ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Mass Spectrometric Method ◽  
High Fat ◽  
Low Fat ◽  
Fasted State ◽  
Tandem Mass Spectrometric ◽  
Fat Meal

Abstract Background: Food can change the bioavailability of a drug, which can have clinically significant consequences. This study was conducted to investigate the effect of food on the oral bioavailability of dasatinib (SPRYCEL®) in healthy adult subjects. Methods: Fifty-four healthy adult subjects received a single dose of dasatinib 100 mg dose, as 2 x 50 mg film-coated tablets after an overnight fast and within 10 minutes after the ingestion of a low-fat meal (315 kcal [20% fat, 68% carbohydrates, and 12% protein]) and a high-fat meal (985 kcal [52% fat, 34% carbohydrates, and 14% protein]) in a randomly assigned sequence. Individual treatments were separated by at least a 7-day washout period. Serial blood samples were collected for 24 hours after each treatment to determine dasatinib plasma concentrations using a validated liquid chromatography/tandem mass spectrometric method. Dasatinib pharmacokinetic (PK) parameters were determined using a non-compartmental method. Safety was monitored throughout the study. Results: Of the 54 healthy adult subjects (85% male, 61% Caucasian, mean age 32 y, and weight 80 kg), 48 completed the study. There were no serious adverse events. Adverse events and laboratory abnormalities were, in general, typical of those seen with dasatinib administration. PK results are summarized in the table below. Conclusions: Compared to the fasted state, a low-fat meal decreased Cmax and AUC of dasatinib by 21%; a high-fat meal decreased Cmax by 24% and increased AUC by 14%. These results are not expected to be of clinical relevance and, therefore, dasatinib may be taken without regard to meals. The drug was generally safe and well-tolerated when administered in the fed or fasted state. Statistical Analysis of PK Parameters for Dasatinib Treatment PK Parameter Geometric Mean Ratios (95% Confidence Intervals) Fed versus Fasted Low-Fat Meal Cmax 1.216 (1.047, 1.413) AUC 1.212 (1.100, 1.336) High-Fat Meal Cmax 0.758 (0.651, 0.882) AUC 1.140 (1.034, 1.257)

Leptin secretion after a high-fat meal in normal-weight rats: strong predictor of long-term body fat accrual on a high-fat diet

2006 ◽  
Vol 290 (2) ◽  
pp. E258-E267 ◽  
Author(s):  
S. F. Leibowitz ◽  
G.-Q. Chang ◽  
J. T. Dourmashkin ◽  
R. Yun ◽  
C. Julien ◽  
...  
Keyword(s):  
Body Fat ◽  
High Fat Diet ◽  
Strong Predictor ◽  
Normal Weight ◽  
Sprague Dawley ◽  
High Fat ◽  
Sprague Dawley Rats ◽  
Orexigenic Peptide ◽  
Fat Meal

The objective of this study was to investigate meal-related endocrine changes that permit one to identify Sprague-Dawley rats at normal weight that are prone (OP) vs. resistant (OR) to obesity. In blood collected via chronic cardiac catheters, a 2-h high-fat meal (HFM, 50% fat, 40 kcal) at dark onset caused a significant increase in leptin, insulin, and triglycerides compared with premeal levels. Similar to patterns in already obese compared with lean rats on a high-fat diet, these meal-induced endocrine changes in normal-weight rats on lab chow were almost twofold larger in OP rats that, compared with OR rats, subsequently accumulated 100% more fat mass on a chronic high-fat diet. These exaggerated endocrine changes were similarly observed in blood collected using a simpler tail vein puncture procedure. In three separate experiments, the HFM-induced rise in leptin was found to be the strongest, positive correlate ( r = +0.58, +0.62 and +0.64) of long-term body fat accrual. The lowest (2–5 ng/ml) vs. highest (6–9 ng/ml) scores for this post-HFM leptin measurement identified distinct OR and OP subgroups, respectively, when they were similar in body weight (340–350 g), premeal leptin (2.6–3.4 ng/ml), and meal size (40 kcal). Subsequent tests in these normal-weight OP rats revealed a distinct characteristic compared with OR rats, namely, exaggerated HFM-induced rise in expression of the orexigenic peptide galanin in the paraventricular nucleus. Thus, with this HFM-induced leptin measurement, OP rats can be identified while still at normal weight and then investigated for mechanisms that contribute to their excessive body fat accrual on a high-fat diet.

scholarly journals Diurnal trends in responses of blood plasma concentrations of glucose, insulin, and C-peptide following high- and low-fat meals and their relation to fat metabolism in healthy middle-aged volunteers

1997 ◽  
Vol 77 (4) ◽  
pp. 523-535 ◽  
Author(s):  
David L. Frape ◽  
Norman R. Williams ◽  
A. J. Scriven ◽  
Christopher R. Palmer ◽  
Kathryn O'Sullivan ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Fat Metabolism ◽  
Plasma Concentrations ◽  
Insulin Response ◽  
Latin Squares ◽  
Postprandial Blood Glucose ◽  
High Fat ◽  
Middle Aged ◽  
C Peptide ◽  
Fat Meal

An experiment was conducted in twelve healthy middle-aged volunteers, six of each sex, with a mean BMI of 27kg/m2 to detect differences between morning and afternoon in postprandial blood glucose, insulin and C-peptide concentrations. These responses were measured following the consumption of isoenergetic meals that were high or low in fat content, at breakfast and at lunch. Over 4d each subject received the high-carbohydrate (L, 5·5 g mixed fat/meal) and moderately high-fat (M, 33 g mixed fat/meal) breakfasts and lunches, in three combinations (LL, MM, LM), or they fasted at breakfast time and received a moderately high-fat lunch (NM), in three Latin squares. Each evening a standard meal was given. Plasma glucose, insulin and C-peptide responses were greater following L than M meals and within both MM and LL treatments insulin and C-peptide responses were greater following breakfast than following lunch. The incremental C-peptide response to a fatty lunch following a fast at breakfast time (NM) was similar to that to a fatty breakfast, but the incremental insulin response for the same comparison was marginally lower at lunch (P=0·06). The relationship of C-peptide and insulin concentrations was assessed. Plasma glucose response to a fatty lunch was increased by a fatty breakfast. The relationships of these metabolic events with fat metabolism are discussed.

scholarly journals The Lidose Hard Capsule Formulation of Fenofibrate is Suprabioavailable Compared to the Nanoparticle Tablet Formulation Under High-fat Fed Conditions

2015 ◽  
Vol 18 (1) ◽  
pp. 61 ◽  
Author(s):  
Roger K Verbeeck ◽  
Sophie De Niet ◽  
Sonia Lebrun ◽  
Mickael Tremege ◽  
Tim W. Rennie ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Plasma Concentrations ◽  
Relative Bioavailability ◽  
Fenofibric Acid ◽  
High Fat ◽  
Case Scenario ◽  
Capsule Formulation ◽  
Worst Case ◽  
Randomized Crossover Study ◽  
Fat Meal

Purpose: The therapeutic equivalence of multiple registered fenofibrate formulations, several of which are suprabioavailable and therefore marketed at lower dosage strengths than their reference products, is based on the results of bioequivalence studies. Most of these formulations show a higher bioavailability when taken with a high-fat meal. The relative bioavailability of two of these formulations, the 200 mg Lidose hard capsules and the 145 mg nanoparticle tablets, was assessed when taken with a high-fat meal. Methods: In this single dose, 2-way, randomized, crossover study, 24 healthy subjects received a 200 mg fenofibrate Lidose hard capsule (Test) and a 145 mg nanoparticle tablet (Reference) under high-fat fed conditions. Plasma concentrations of fenofibric acid were measured up to 72 hours by using a validated LC-MS/MS method. Results: The geometric mean ratios (Test/Reference) and the 90% confidence intervals for AUC0-t and Cmax were 1.37 (131.58 – 142.88) and 1.38 (124.60 – 152.93), respectively. The median (range) Tmax­ values of fenofibric acid were 4.5 h (3.0 – 8.0 h) and 3.25 h (1.0 – 6.5 h) after administration of the Lidose hard capsule and the nanoparticle tablet, respectively. Conclusion: Under high-fat fed conditions the extent of fenofibrate absorption was 37% higher for the 200 mg Lidose hard capsule compared to the 145 mg nanoparticle tablet, which is exactly as expected based on a mg-to-mg weight basis. The results of the present study underline the importance of assessing bioequivalence of fenofibrate formulations under identical fed conditions, and preferentially after a high-fat meal as this condition represents the worst-case scenario. Furthermore, the results of this study demonstrate that the 145 mg nanoparticle tablet is not bioequivalent to the 200 mg Lidose hard capsule when administered under high-fat meal conditions.  This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Effects of high- and low-fat meals on the diurnal response of plasma lipid metabolite concentrations in healthy middle-aged volunteers

1997 ◽  
Vol 77 (3) ◽  
pp. 375-390 ◽  
Author(s):  
D. L. Frape ◽  
N. R. Williams ◽  
A. J. Scriven ◽  
C. R. Palmer ◽  
Kathryn O'sullivan ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Plasma Lipid ◽  
Hdl Cholesterol ◽  
Blood Lipid ◽  
Tolerance Test ◽  
Cholesterol Concentration ◽  
High Fat ◽  
Middle Aged ◽  
Low Fat ◽  
Fat Meal

Three experiments were conducted in healthy middle-aged volunteers (six males and six females in Expt 1, six males and two females in Expt 2 and twelve males in Expt 3) with a mean BMI of 27 kg/m2 to determine whether there is a difference between morning and afternoon dietary fat clearance and utilization, and to determine in what way the fat and starch contents of the meal influence postprandial blood lipid metabolites over 4·5 h. Over 4 days in Expt 1 each subject received isoenergetic, high-carbohydrate (L, 5·5 g mixed fat/meal) and moderately high-fat (M, 33 g mixed fat/meal) breakfasts and lunches, in three combinations (LL, MM, LM), or they fasted at breakfast time and received a high fat lunch (NM) in a randomized and balanced arrangement. Each evening a standard meal was given. The following effects were significant (P<0·05): plasma triacylglycerol (TAG) responses were greater following M meals; plasma TAG concentrations were greater in the afternoon than in the morning, following two meals of the same composition, although the postprandial incremental response was less following lunch than following breakfast and peak responses were reached much earlier than after breakfast; a low-fat breakfast, or fasting at breakfast time, delayed the peak TAG response to a M lunch. The plasma concentrations of non-esterified fatty acids (NEFA) and of free glycerol were higher in the afternoon following M meals at breakfast and lunch, especially in males. This response was reduced, by the L breakfast preceding the M lunch. Two M meals in succession lowered plasma HDL-cholesterol concentration. In Expt 2 each subject received a very low-fat (VL) breakfast, followed by a lunch of the same composition. Each of these meals was followed, 110 min from the start of eating, by an infusion of Intralipid 10% emulsion at the rate of 1 ml/kg body weight over 60 s. Clearance rates of Intralipid were faster in the afternoon than in the morning (P= 0·024). In Expt 3 twelve subjects were randomly allocated to either treatment MM or LM meal patterns, as given in Expt 1. These were given daily for a period of 17 d, during which the change in fasting plasma TAG concentration was similar in both treatments. On days 1, 16 and 17 responses were measured to the M lunch and to a glucose tolerance test (GTT), conducted 2 h 17 min after lunch. The post-lunch responses confirmed those found in Expt 1; but immediately following the glucose dose there was an abrupt increase in plasma TAG that was greater in treatment LM than in treatment MM (P= 0·025), whereas plasma NEFA concentration decreased rapidly in both treatments at that time (P = 0·00066)

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