Metabolic and Inflammatory Responses to Different Caloric Loads of a High-Fat Meal Are Distinct between Normal-Weight and Obese Individuals

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.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.4.e549 ◽

1994 ◽

Vol 267 (4) ◽

pp. E549-E559 ◽

Cited By ~ 13

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.

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Manipulation of fatty acid composition in a high-fat meal does not result in differential alterations in appetite or food intake in normal weight females: A single-blind randomized crossover study

Appetite ◽

10.1016/j.appet.2020.105085 ◽

2021 ◽

Vol 160 ◽

pp. 105085

Author(s):

Austin J Graybeal ◽

Meena Shah ◽

Jada L. Willis

Keyword(s):

Fatty Acid Composition ◽

Fatty Acid ◽

Food Intake ◽

Crossover Study ◽

Acid Composition ◽

Normal Weight ◽

High Fat ◽

Single Blind ◽

Randomized Crossover Study ◽

Fat Meal

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Endothelial inflammation correlates with subject triglycerides and waist size after a high-fat meal

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01036.2010 ◽

2011 ◽

Vol 300 (3) ◽

pp. H784-H791 ◽

Cited By ~ 31

Author(s):

Ying I. Wang ◽

John Schulze ◽

Nadine Raymond ◽

Tyler Tomita ◽

Kayan Tam ◽

...

Keyword(s):

Waist Circumference ◽

Inflammatory Responses ◽

Ex Vivo ◽

High Fat ◽

Membrane Expression ◽

Serum Triglycerides ◽

Endothelial Inflammation ◽

Tnf Α ◽

Postprandial Triglyceride ◽

Fat Meal

A rise in postprandial serum triglycerides (PP-sTG) can potentiate inflammatory responses in vascular endothelial cells (ECs) and thus serves as an independent risk factor for predicting increased cardiovascular morbidity. We examined postprandial triglyceride-rich lipoproteins (PP-TGRLs) in subjects ranging from normal to hypertriglyceridemic for their capacity to alter EC acute inflammatory responses. Cultured human aortic ECs (HAECs) were conditioned with PP-TGRLs isolated from human serum at the peak after a moderately high-fat meal. VLDL particle size increased postprandially and varied directly with the subject's PP-sTG level and waist circumference. PP-TGRL particles bound to HAECs and were internalized via LDL receptor-mediated endocytosis. PP-TGRL alone did not induce an inflammatory response over the range of individuals studied. However, combined with low-dose TNF-α stimulation (0.3 ng/ml), it elicited a net 10–15% increase above cytokine alone in the membrane expression of VCAM-1, ICAM-1, and E-selectin, which was not observed with fasting TGRLs. In contrast to upregulation of ICAM-1 and E-selectin, VCAM-1 transcription and expression varied in direct proportion with individual PP-sTG and waist circumference. The extent of monocyte arrest on inflamed HAECs under shear stress also correlated closely with VCAM-1 expression induced by conditioning with PP-TGRL and TNF-α stimulation. This ex vivo approach provides a quantitative means to assess an individual's inflammatory potential, revealing a greater propensity for endothelial inflammation in hypertriglyceridemic individuals with abdominal obesity.

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Abstract 629: Sensing Nutrient Overload: The Role of the Endothelium

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.629 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Kyle Preston ◽

Rosario Scalia

Keyword(s):

Visceral Fat ◽

Inflammatory Responses ◽

High Fat ◽

Low Fat ◽

Fat Depots ◽

Leukocyte Population ◽

Mesenteric Fat ◽

Fat Pads ◽

Fat Meal

Recent data suggest that leukocyte accumulation into visceral fat depots occurs within 72 following high fat feeding. At this early stage, neutrophils have been found to be the predominant leukocyte population to infiltrate the visceral fat. Other studies have shown that deletion of the high affinity counter-receptor for P-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), attenuate immune cell infiltration into fat depots of chronically high fat fed mice. Accordingly, we tested the hypothesis that endothelial, expressed P-selectin serves as a molecular sensor for initiating inflammatory responses in the microcirculation of the visceral fat following nutrient overload. Wild-type (WT) and P-sel-/- C57BL/6 mice were given either a low fat (10% fat) or a high fat (60% fat) meal by gavage. All mice were studied 1, 2, 3, 4 and 24 hours post gavage by intravital microscopy (IVM) to measure postprandial kinetics of leukocyte rolling (LR) and leukocyte adhesion (LA) in the microcirculation of the mesenteric fat pads. In WT mice, administration of high fat meals acutely and transiently increased LR and LA in the visceral fat microcirculation (p<0.001 vs low fat meal). In contrast, high fat meals failed to increase LR and LA in P-sel-/- mice (NS vs low fat meal WT). Immunofluorescence studies demonstrated that fat meals upregulate cell surface expression of P-selectin in the visceral fat microcirculation, but not in the subcutaneous one. Flow cytometry studies demonstrated that neutrophils are the main leukocyte population to acutely infiltrate visceral fat depots after lipid overload. Mechanistic studies were also undertaken using palmitate, a postprandially elevated, unsaturated free fatty acid. Superfusion of (dose) palmitate during IVM acutely increased LR and LA in the microcirculation of the mesenteric fat pads of WT mice (p<0.01 vs control), a response that was prevented in vivo by P-selectin antibody blockade. Taken together, these data demonstrate that endothelial P-selectin plays a key role in the early inflammatory responses to fat overload by promoting neutrophil trafficking in the microcirculation of the visceral fat. These data first uncover a novel nutrient-sensory role of the vascular endothelium, which warrants further investigation.

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