Recent Advances in Triacylglycerol Mobilization by the Gut

Xiao, Changting; Stahel, Priska; Carreiro, Alicia L.; Buhman, Kimberly K.; Lewis, Gary F.

doi:10.1016/j.tem.2017.12.001

Cited by 63 publications

(46 citation statements)

References 91 publications

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“…These droplets appear to act as a 'buffer' to allow rapid fat uptake from the diet and controlled release of lipoprotein particles. Thus, the apoB48 synthesis and secretion we observed in subjects 12 h after food intake could have been associated with lipid-poor particles [47] or triglyceride transporting particles assembled using lipid stored in cytoplasmic droplets [48]. Further metabolic investigations will be required to distinguish between these possibilities.…”

Section: Discussionmentioning

confidence: 94%

Investigation of human apoB48 metabolism using a new, integrated non‐steady‐state model of apoB48 and apoB100 kinetics

et al. 2019

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BackgroundTriglyceride‐rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low‐density lipoproteins (VLDL).MethodsMass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL 1 and VLDL 2 density intervals. An integrated non‐steady‐state multicompartmental model was constructed to describe the metabolism of apoB48‐ and apoB100‐containing lipoproteins following a fat‐rich meal, as well as during prolonged fasting.ResultsThe kinetic model described the metabolism of apoB48 in CM, VLDL 1 and VLDL 2. It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL 1 and VLDL 2. ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50 mg day−1, and the increment during absorption was about 230 mg day−1. The fractional catabolic rates for apoB48 in VLDL 1 and VLDL 2 were substantially lower than for apoB48 in CM.DiscussionThis novel non‐steady‐state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.

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Section: Discussionmentioning

confidence: 94%

Investigation of human apoB48 metabolism using a new, integrated non‐steady‐state model of apoB48 and apoB100 kinetics

et al. 2019

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“…CLDs expand in size following a fat meal via either fusion or TG synthesis at the CLD surface, while CLD catabolism during the post-absorptive state occurs through TG lipolysis and redistribution or lipophagy. CLDs may serve as transient storage of TG in enterocytes, which attenuates postprandial TG excursion and provides a continuous TG supply as substrates for late postprandial and post-absorptive CM secretion (Beilstein et al, 2015), enhances the overall efficiency of dietary fat absorption, and prevents cellular and systemic toxicity as a result of lipid overload (Xiao et al, 2018a). It is noted that temporary lipid storage in CLDs is conserved and common in lower species, such as Caenorhabditis elegans and reptiles, implicating evolutionary benefits.…”

Section: Dietary Tg Digestion Absorption and Chylomicron Synthesis mentioning

confidence: 99%

“…While the majority of dietary TGs are rapidly secreted in CMs during meal ingestion, evidence supports more prolonged retention of TGs in the intestine during the post-absorptive period, with subsequent release triggered by a number of factors (Xiao et al, 2018a(Xiao et al, , 2019a. In healthy, lean individuals, postprandial plasma TGs rapidly rise, typically peak at 3-4 h after meal, and gradually return to fasting level after 6-8 h. However, under certain circumstances such as ingestion of a second fat meal or glucose, many hours after lipid ingestion, release of TGs from an intestinal "storage" pool can be demonstrated (Xiao et al, 2019a).…”

Section: Lipid Retention and Mobilization Prolonged Post-absorptive Lmentioning

confidence: 99%

Emerging Role of Lymphatics in the Regulation of Intestinal Lipid Mobilization

et al. 2020

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Intestinal handling of dietary triglycerides has important implications for health and disease. Following digestion in the intestinal lumen, absorption, and re-esterification of fatty acids and monoacylglycerols in intestinal enterocytes, triglycerides are packaged into lipoprotein particles (chylomicrons) for secretion or into cytoplasmic lipid droplets for transient or more prolonged storage. Despite the recognition of prolonged retention of triglycerides in the post-absorptive phase and subsequent release from the intestine in chylomicron particles, the underlying regulatory mechanisms remain poorly understood. Chylomicron secretion involves multiple steps, including intracellular assembly and postassembly transport through cellular organelles, the lamina propria, and the mesenteric lymphatics before being released into the circulation. Contrary to the long-held view that the intestinal lymphatic vasculature acts mainly as a passive conduit, it is increasingly recognized to play an active and regulatory role in the rate of chylomicron release into the circulation. Here, we review the latest advances in understanding the role of lymphatics in intestinal lipid handling and chylomicron secretion. We highlight emerging evidence that oral glucose and the gut hormone glucagon-like peptide-2 mobilize retained enteral lipid by differing mechanisms to promote the secretion of chylomicrons via glucose possibly by mobilizing cytoplasmic lipid droplets and via glucagon-like peptide-2 possibly by targeting post-enterocyte secretory mechanisms. We discuss other potential regulatory factors that are the focus of ongoing and future research. Regulation of lymphatic pumping and function is emerging as an area of great interest in our understanding of the integrated absorption of dietary fat and chylomicron secretion and potential implications for whole-body metabolic health.

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“…At the ER, TG is re‐synthesized and is either processed into cytoplasmic lipid droplets (CLD) or pre‐mature chylomicrons (pre‐CM). Enterocyte CLD have been shown in mice to act as temporary storage vesicles during periods of high postprandial fat influx, likely to decrease enterocyte lipid overload‐induced toxicity 6,7 . CLD are eventually mobilized, undergoing TG hydrolysis and CM synthesis, clearing from enterocytes over a period of up to 12 hours 6,8 .…”

Section: Introductionmentioning

confidence: 99%

Requirement for the intestinal epithelial insulin‐like growth factor‐1 receptor in the intestinal responses to glucagon‐like peptide‐2 and dietary fat

et al. 2020

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Abbreviations: APO, apolipoprotein; CD36, cluster-of-differentiation 36; DFTT, duodenal fat tolerance test; FATP-4, fatty acid transfer protein-4; h(GLY 2 ) GLP-2, human glycine 2 -glucagon-like peptide-2; IE-IGF-1R, intestinal epithelial-insulin-like growth factor-1 receptor; KO, knockout; MTP, microsomal triglyceride transfer protein; OFTT, oral fat tolerance test; WD, Western diet. AbstractThe intestinal hormone, glucagon-like peptide-2 (GLP-2), enhances the enterocyte chylomicron production. However, GLP-2 is known to require the intestinal-epithelial insulin-like growth factor-1 receptor (IE-IGF-1R) for its other actions to increase intestinal growth and barrier function. The role of the IE-IGF-1R in enterocyte lipid handling was thus tested in the GLP-2 signaling pathway, as well as in response to a Western diet (WD). IE-IGF-1R knockout (KO) and control mice were treated for 11 days with h(GLY 2 )GLP-2 or fed a WD for 18 weeks followed by a duodenal fat tolerance test with C 14 -labeled triolein. Human Caco-2BBE cells were treated with an IGF-1R antagonist or signaling inhibitors to determine triglyceride-associated protein expression. The IE-IGF-1R was required for GLP-2-induced increases in CD36 and FATP-4 in chow-fed mice, and for expression in vitro; FATP-4 also required PI3K/Akt. Although WD-fed IE-IGF-1R KO mice demonstrated normal CD36 expression, the protein was incorrectly localized 2h post-duodenal fat administration.IE-IGF-1R KO also prevented the WD-induced increase in MTP and decrease in APOC3, increased jejunal mucosal C 14 -fat accumulation, and elevated plasma triglyceride and C 14 -fat levels. Collectively, these studies elucidate new roles for the IE-IGF-1R in enterocyte lipid handling, under basal conditions and in response to GLP-2 and WD-feeding.

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Recent Advances in Triacylglycerol Mobilization by the Gut

Cited by 63 publications

References 91 publications

Investigation of human apoB48 metabolism using a new, integrated non‐steady‐state model of apoB48 and apoB100 kinetics

Investigation of human apoB48 metabolism using a new, integrated non‐steady‐state model of apoB48 and apoB100 kinetics

Emerging Role of Lymphatics in the Regulation of Intestinal Lipid Mobilization

Requirement for the intestinal epithelial insulin‐like growth factor‐1 receptor in the intestinal responses to glucagon‐like peptide‐2 and dietary fat

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