Lipid absorption and overall intestinal lymphatic transport are impaired following partial small bowel resection in mice

Abstract Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal fatty acid uptake and transport. C57BL6 and Prox1 creER-Rosa26LSLTdTomato (lymphatic reporter) mice underwent 50% or 75% proximal SBR or sham operations. Functional transport of lipids and fecal fat content was measured and lymphatic vasculature was compared via imaging. There was a significant reduction in functional transport of cholesterol and triglyceride after SBR with increasing loss of bowel, mirrored by a progressive increase in fecal fat content. We also describe significant morphological changes in the lymphatic vasculature in both the lamina propria and mesentery. Intestinal lymphatic drainage assay in vivo demonstrated a marked reduction of systemic absorption after resection. Intestinal lymphatic vessels significantly remodel in the setting of chronic SBS. This remodeling results in impaired intestinal transport of fat via the compromised lymphatic architecture, contributing to decreased fatty acid uptake. We believe that these changes may contribute to the development of IFALD, a major morbidity in patients with SBS.

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Proteomic Analysis of the Intestinal Adaptation Response Reveals Altered Expression of Fatty Acid Binding Proteins Following Massive Small Bowel Resection

Journal of Proteome Research ◽

10.1021/pr900976f ◽

2010 ◽

Vol 9 (3) ◽

pp. 1437-1449 ◽

Cited By ~ 17

Author(s):

Andrew N. Stephens ◽

Prue M. Pereira-Fantini ◽

Guineva Wilson ◽

Russell G. Taylor ◽

Adam Rainczuk ◽

...

Keyword(s):

Fatty Acid ◽

Small Bowel ◽

Bowel Resection ◽

Intestinal Adaptation ◽

Small Bowel Resection ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Binding ◽

Altered Expression ◽

Adaptation Response ◽

Massive Small Bowel Resection

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Increased Liver Fatty Acid Uptake Is Partly Reversed and Liver Fat Content Normalized After Bariatric Surgery

Diabetes Care ◽

10.2337/dc17-0738 ◽

2017 ◽

Vol 41 (2) ◽

pp. 368-371 ◽

Cited By ~ 14

Author(s):

Heidi Immonen ◽

Jarna C. Hannukainen ◽

Nobuyuki Kudomi ◽

Jussi Pihlajamäki ◽

Virva Saunavaara ◽

...

Keyword(s):

Bariatric Surgery ◽

Fatty Acid ◽

Fatty Acid Uptake ◽

Fat Content ◽

Liver Fat ◽

Acid Uptake ◽

Liver Fatty Acid ◽

Liver Fat Content

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Effect of Weight Loss on Liver Free Fatty Acid Uptake and Hepatic Insulin Resistance

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-1689 ◽

2009 ◽

Vol 94 (1) ◽

pp. 50-55 ◽

Cited By ~ 83

Author(s):

Antti P. M. Viljanen ◽

Patricia Iozzo ◽

Ronald Borra ◽

Mikko Kankaanpää ◽

Anna Karmi ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Fatty Acid ◽

Free Fatty Acid ◽

Fatty Acid Uptake ◽

Fat Content ◽

Liver Fat ◽

Hepatic Insulin Resistance ◽

Acid Uptake ◽

Liver Fat Content

Abstract Objective: Weight loss has been shown to decrease liver fat content and whole-body insulin resistance. The current study was conducted to investigate the simultaneous effects of rapid weight reduction with a very-low-calorie diet on liver glucose and fatty acid metabolism and liver adiposity. Hypothesis: We hypothesized that liver insulin resistance and free fatty acid uptake would decrease after weight loss and that they are associated with reduction of liver fat content. Design: Thirty-four healthy obese subjects (body mass index, 33.7 ± 8.0 kg/m2) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [18F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [18F]fluoro-6-thia-heptadecanoic acid and positron emission tomography. Liver volume and fat content were measured using magnetic resonance imaging and spectroscopy. Results: Subjects lost weight (11.2 ± 2.9 kg; P < 0.0001). Liver volume decreased by 11% (P < 0.002), which was partly explained by decreased liver fat content (P < 0.0001). Liver free fatty acid uptake was 26% lower after weight loss (P < 0.003) and correlated with the decrement in liver fat content (r = 0.54; P < 0.03). Hepatic glucose uptake during insulin stimulation was unchanged, but the endogenous glucose production decreased by 40% (P < 0.04), and hepatic insulin resistance by 40% (P < 0.05). Conclusions: The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.

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Development and Physiological Regulation of Intestinal Lipid Absorption. II. Dietary lipid absorption, complex lipid synthesis, and the intracellular packaging and secretion of chylomicrons

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00299.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. G645-G650 ◽

Cited By ~ 79

Author(s):

Charles M. Mansbach ◽

Fred Gorelick

Keyword(s):

Fatty Acid ◽

Lipid Synthesis ◽

Clinical Importance ◽

Fatty Acid Uptake ◽

The United States ◽

Dietary Lipid ◽

Lipid Absorption ◽

Acid Uptake ◽

Fatty Acid Binding ◽

Transport Vesicle

Research in dietary fat absorption has developed urgency because of the widely recognized epidemic of obesity in the United States. Despite its clinical importance, many controversies exist over some of the basic aspects of this process from the mechanisms of fatty acid uptake to the control of triacylglycerol export in chylomicrons. Recent advances have included the identification of a number of fatty acid transporters, the discovery of families of acyl-CoA synthetase long chains and acyltransferases, a physiological function for liver-fatty acid binding protein, and the characterization of the prechylomicron transport vesicle transporting chylomicrons from the endoplasmic reticulum to the Golgi.

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Inhibition of Intestinal Lipid Absorption by Cyanobacterial Strains in Zebrafish Larvae

Marine Drugs ◽

10.3390/md19030161 ◽

2021 ◽

Vol 19 (3) ◽

pp. 161

Author(s):

Marta Bellver ◽

Susana Lemos da Costa ◽

Begoña Astrain Sanchez ◽

Vitor Vasconcelos ◽

Ralph Urbatzka

Keyword(s):

Fatty Acid ◽

Fatty Acid Uptake ◽

Dietary Lipid ◽

Chain Fatty Acid ◽

Lipid Absorption ◽

Whole Body ◽

Acid Uptake ◽

Protease Inhibition ◽

Zebrafish Larvae

Obesity is a complex metabolic disease, which is increasing worldwide. The reduction of dietary lipid intake is considered an interesting pathway to reduce fat absorption and to affect the chronic energy imbalance. In this study, zebrafish larvae were used to analyze effects of cyanobacteria on intestinal lipid absorption in vivo. In total, 263 fractions of a cyanobacterial library were screened for PED6 activity, a fluorescent reporter of intestinal lipases, and 11 fractions reduced PED6 activity > 30%. Toxicity was not observed for those fractions, considering mortality, malformations or digestive physiology (protease inhibition). Intestinal long-chain fatty acid uptake (C16) was reduced, but not short-chain fatty acid uptake (C5). Alteration of lipid classes by high-performance thin-layer chromatography (HPTLC) or lipid processing by fluorescent HPTLC was analyzed, and 2 fractions significantly reduced the whole-body triglyceride level. Bioactivity-guided feature-based molecular networking of LC-MS/MS data identified 14 significant bioactive mass peaks (p < 0.01, correlation > 0.95), which consisted of 3 known putative and 11 unknown compounds. All putatively identified compounds were known to be involved in lipid metabolism and obesity. Summarizing, some cyanobacterial strains repressed intestinal lipid absorption without any signs of toxicity and could be developed in the future as nutraceuticals to combat obesity.

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