Intestinal lipid–derived signals that sense dietary fat

DiPatrizio, Nicholas V.; Piomelli, Daniele

doi:10.1172/jci76302

Cited by 88 publications

(66 citation statements)

References 127 publications

(172 reference statements)

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“…Studies in genetically modified mice had implicated CD36, GPR40, GP120 and TRPM5 in fat sensing 107 . However, more recent data question that role of GPR40 and GPR120 in fat 'taste' 108 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Monteiro

Batterham

2017

Gastroenterology

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The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight-reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 (GLP-1) highlights the therapeutic potential of gut-derived signals acting via non-physiological mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage GI signals in order to treat obesity.

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“…Studies in genetically modified mice had implicated CD36, GPR40, GP120 and TRPM5 in fat sensing 107 . However, more recent data question that role of GPR40 and GPR120 in fat 'taste' 108 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Monteiro

Batterham

2017

Gastroenterology

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“…[1,[2][3][4][5][6][7][8][9][10][11][12][13][14] C]ethanolamine HCl was from Moravek Biochemicals (Brea, CA). Horseradish peroxidaselinked anti-mouse and anti-rabbit IgGs were from GE Healthcare (Piscataway, NJ).…”

Section: 2-[1′-mentioning

confidence: 99%

Comparative analyses of isoforms of the calcium-independent phosphatidylethanolamine N-acyltransferase PLAAT-1 in humans and mice

Hussain

Uyama

Kawai

et al. 2016

Journal of Lipid Research

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Fatty acyl ethanolamides [N-acylethanolamines (NAEs)] are a class of lipid mediators. Among them, arachidonoylethanolamide (anandamide) is known to be an endogenous ligand of cannabinoid receptors (namely, an endocannabinoid) (1). In addition, palmitoylethanolamide and oleoylethanolamide show biological activities such as antiinflammation, analgesia, and appetite suppression via different receptors including PPAR- (2-5). These NAEs are biosynthesized principally through a two-step pathway from membrane glycerophospholipids via N-acylphosphatidylethanolamines (NAPEs) (6). The first reaction is the transfer of an acyl chain from a glycerophospholipid molecule such as phosphatidylcholine (PC) to the amino group of phosphatidylethanolamine (PE), resulting in the formation of NAPE, and the enzyme responsible is known as PE N-acyltransferase. Very recently, cPLA 2 ɛ, a member of the cytosolic phospholipase A 2 (PLA 2 ) family (PLA2G4), has been identified as the calcium-stimulated N-acyltransferase capable of catalyzing this step (7). However, a series of our recent studies revealed that five members of the HRAS-like suppressor (HRASLS) family, which were originally discovered as tumor suppressors, possess calciumindependent phospholipid-metabolizing activities including NAPE-forming N-acyltransferase and PLA 1/2 activities (8-12), and we proposed to give HRASLS-1-5 the names phospholipase A/acyltransferase-1-5 (PLAAT-1-5), respectively (11). Among the five members, PLAAT-1 particularly received our attention because of its relatively high PE N-acyltransferase activity over PLA 1/2 activity in vitro and predominant expression in testis, skeletal muscle, brain, and heart of humans, mice, and rats, where NAPEs accumulate in response to ischemia and inflammation (11,13).Abstract N-Acylphosphatidylethanolamines (NAPEs) are a class of glycerophospholipids, which are known as precursors for different bioactive N-acylethanolamines. We previously reported that phospholipase A/acyltransferase-1 (PLAAT-1), which was originally found in mammals as a tumor suppressor, catalyzes N-acylation of phosphatidylethanolamines to form NAPEs. However, recent online database suggested the presence of an uncharacterized isoform of PLAAT-1 with an extra sequence at the N terminus. In the present study, we examined the occurrence, intracellular localization, and catalytic properties of this longer isoform, as well as the original shorter isoform from humans and mice. Our results showed that human tissues express the longer isoform but not the short isoform at all. In contrast, mice expressed both isoforms with different tissue distribution. Unlike the cytoplasmic localization of the shorter isoform, the long isoform was found in both cytoplasm and nucleus, inferring that the extra sequence harbors a nuclear localization signal. As assayed with purified proteins, neither isoform required calcium for full activity. Moreover, the overexpression of each isoform remarkably increased cellular NAPE levels. These results conclude that the new long is...

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“…10,11 Though the gut is richly innervated, sensory nerves do not penetrate the GI epithelium and so luminal sensing mechanisms have developed to transduce information about the presence and nature of nutrients in the gut. [12][13][14] These 'tasting' mechanisms involve the expression of taste receptors, similar to those of the tongue, and other mechanisms that detect and transduce luminal signals. In addition, there are also receptors for bacteria and bacterial products, notably free fatty acids and other metabolites, which are also sensed as part of the luminal detection systems.…”

Section: Ka Sharkeymentioning

confidence: 99%

Targeting the gut to treat obesity and its metabolic consequences: view from the Chair

Sharkey

2016

Int J Obes Supp

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The neurohumoral signaling systems of the gastrointestinal (GI) tract are considered the most significant of the peripheral inputs controlling both food intake in the short term and energy balance over a longer time course. The importance of the GI tract in the control of energy balance is underscored by the marked beneficial effects of bariatric surgeries for the treatment of obesity. Despite their effectiveness, the mechanisms of bariatric surgery remain to be fully elucidated. Considerable new evidence points to the importance of gut-brain communication, gut barrier function and microbial signaling as three of the most important mechanisms of bariatric surgery-induced weight loss. These mechanisms are reviewed in the present article and the accompanying four papers.International Journal of Obesity Supplements (2016) 6, S3-S5; doi:10.1038/ijosup.2016.2Obesity and its metabolic complications remain one of the most challenging health issues facing society today. The rapidity with which shifts in the average weight of populations have increased since the late 1970s is remarkable. For example, in Canadian adults, rates of obesity have more than doubled from around 10% in the early 1970s to~25% today. 1-3 Similar trends have been seen around the world. These rapid shifts in weight over such a short time suggest that changes in diet, lifestyle and/or other environmental factors have a critical role in the expression of obesity. Although genetic factors may confer vulnerability (or protection) towards obesity, these are not likely to be the dominant cause of obesity in the majority of people.Obesity is ultimately caused by a state of positive energy balance. Whilst energy expenditure is an important determinant of overall energy balance, excessive energy intake is generally regarded as the major determinant of obesity. 4 There are numerous peripheral and central nervous system signaling systems involved in the regulation of food intake and energy balance. Of these, the neurohumoral signaling systems of the gastrointestinal (GI) tract are considered the most significant of the peripheral inputs controlling both food intake in the short term and energy balance over a longer time course. 5,6 Gut-derived signals impact other peripheral organs and tissues, such as the liver and adipose tissue, influencing their functions in ways that may increase or reduce the propensity for obesity. 5 The importance of the GI tract in the control of energy balance is underscored by the marked effects of bariatric surgery. 7,8 Altering the manner and quantity with which food is delivered to the small intestine either by greatly limiting the size of the stomach (as in vertical sleeve gastrectomy) or bypassing the majority of the stomach (as in Roux-en-Y gastric bypass) leads to marked and sustained reductions in body weight. 8,9 Considerable research effort has been expended to determine the mechanisms underlying the remarkable effects of bariatric surgery and the articles that follow this overview review much of the current thinking on th...

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Intestinal lipid–derived signals that sense dietary fat

Cited by 88 publications

References 127 publications

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Comparative analyses of isoforms of the calcium-independent phosphatidylethanolamine N-acyltransferase PLAAT-1 in humans and mice

Targeting the gut to treat obesity and its metabolic consequences: view from the Chair

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