Intestinal Absorption Of Fatty Acids Research Articles

Preparation and Characterization of Fish Oil Pickering Emulsions Stabilized by Resveratrol-Loaded Gliadin/Chitin Nanocrystal Composite Nanoparticles.

Unsaturated fatty acids present in fish oil offer various physiological benefits to the human body. However, their susceptibility to oxidation severely limits their potential applications. The purpose of this study was to develop Pickering emulsions stabilized from a composite of resveratrol-loaded gliadin nanoparticles and oxidized chitin nanocrystals (GR/OC) to protect fish oil from oxidation. The effects of the GR/OC composite on the characterizations of fish oil Pickering emulsions were investigated, including the microstructure, physicochemical properties (stability and rheological behavior), and digestion properties in vitro. The results revealed that an increased concentration of the GR/OC composite significantly reduced the droplet size and improved the ambient stability of the emulsions (in terms of pH, ionic strength, temperature, and storage time). Confocal laser scanning microscopy images depicted that the GR/OC nanoparticles were uniformly dispersed at the interface between water and fish oil (W-O interface). This distribution formed a protective envelope around the droplets. Remarkably, the addition of 2% GR/OC nanoparticles stabilized the Pickering emulsions and showed the most positive effect on the antioxidant capacity compared to that of the control group. These stabilized emulsions maintained lower peroxide values and acid values, which were 1.5 times less than those of the blank control during the 14 day accelerated oxidation experiment. Furthermore, the Pickering emulsions stabilized by GR/OC nanoparticles exhibited the ability to protect fish oil from contamination by gastric juices and facilitate the intestinal absorption of omega-3 polyunsaturated fatty acids. The findings suggest that these GR/OC-stabilized Pickering emulsions offer a promising alternative for delivering fish oils in various industries, including the food industry.

PFOA/PFOS Facilitated Intestinal Fatty Acid Absorption by Activating the PPARα Pathway: Insights from Organoids Model.

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) continue to be extensively present in the natural environment and seriously threaten human health. The intestinal tract is the primary organ of PFOA/PFOS exposure due to the consumption of contaminated food and drinking water. However, it remains unclear how PFOA/PFOS affects intestinal function and overall health. The aim of this study was to investigate the influence of PFOA/PFOS on the absorption of fatty acids in the intestine and the underlying mechanisms using three-dimensional (3D) intestinal organoids. Our results showed that PFOS, but not PFOA, could significantly enhance the fatty acid uptake capacity without obvious damage to the organoids. Furthermore, PFOS markedly reduced the protein levels of ChgA in enteroendocrine cells, but with no observed impact on aldolase B+ enterocytes. Mechanistically, exposure to PFOS induced the activation of the peroxisome proliferator-activated receptor (PPAR) α pathway in intestinal organoids, with enhanced expression of PPARα target genes associated with fatty acid metabolism, such as Fabp1 and Cd36 (fatty acid transporter genes), Acox1 and Pdk4 (fatty acid oxidation genes), and Plin2 and Plin3 (lipid droplet synthesis genes). These data suggest that PFOS have the potential to affect the absorption function of the intestinal epithelium through the PPARα pathway, and its effect is much stronger than that of PFOA. Our findings also highlight that organoids can be used as a valuable model for conducting toxicological research on environmental chemicals.

Sulfosuccinimidyl oleate ameliorates the high-fat diet-induced obesity syndrome by reducing intestinal and hepatic absorption.

Background: A high-fat Western diet is a risk factor for obesity and steatosis. Reducing intestinal absorption of a high-fat diet (HFD) is a feasible strategy to control obesity. Sulfosuccinimidyl oleate (SSO) inhibits intestinal fatty acid transport. Therefore, the aim of this study was to investigate the effects of SSO on HFD-induced glucose and lipid metabolism in mice and its possible underlying mechanisms. Methods: Male C57/BL were fed a HFD (60% calories) for 12weeks and were administered an oral dose of SSO (50mg/kg/day). The expression of lipid absorption genes (CD36, MTTP, and DGAT1) and the serum levels of triglycerides (TGs), total cholesterol (TC), and free fatty acids (FFAs) were detected. Lipid distribution in the liver was detected by oil red and hematoxylin and eosin staining. In addition, serum levels of inflammatory factors, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured to detect side effects. Results: SSO was effective in the treatment of obesity and metabolic syndrome induced by HFD in mice. It attenuated the assembly of intestinal epithelial chylomicrons by inhibiting intestinal epithelial transport and absorption of fatty acids, thereby reducing the gene expression levels of MTTP and DGAT1, resulting in decreased plasma TG and FFA levels. At the same time, it inhibited the transport of fatty acids in the liver and improved the steatosis induced by a HFD. The results of oil red staining showed that SSO treatment can reduce lipid accumulation in the liver by 70%, with no drug-induced liver injury detected on the basis of interleukin-6, C-reactive protein, ALT, and AST levels. In addition, SSO treatment significantly improved insulin resistance, decreased fasting blood glucose levels, and improved glucose tolerance in HFD-fed mice. Conclusion: SSO is effective in the treatment of obesity and metabolic syndrome induced by a HFD in mice. SSO reduces intestinal fatty acid absorption by reducing the inhibition of intestinal CD36 expression, followed by decreased TG and FFA levels, which attenuates HFD-induced fatty liver.

Trimethylamine increases intestinal fatty acid absorption: in vitro studies in a Caco-2 cell culture system.

Although elevated blood levels of trimethylamine N-oxide (TMAO) have been associated with atherosclerosis development in humans, the role of its gut microbiota-derived precursor, TMA, in this process has not been yet deciphered. Taking this into account, and the fact that increased intestinal fatty acid absorption contributes to atherosclerosis onset and progression, this study aimed to evaluate the effect of TMA on fatty acid absorption in a cell line that mimics human enterocytes. Caco-2 cells were treated with TMA 250 μM for 24 h. Fatty acid absorption was assessed by measuring the apical-to-basolateral transport and the intracellular levels of BODIPY-C12, a fluorescently labelled fatty acid analogue. Gene expression of the main intestinal fatty acid transporters was evaluated by real-time quantitative reverse transcription PCR. Compared to control conditions, TMA increased, in a time-dependent manner and by 20-50%, the apical-to-basolateral transport and intracellular levels of BODIPY-C12 fatty acid in Caco-2 cells. Fatty acid transport protein 4 (FATP4) and fatty acid translocase (FAT)/CD36 gene expression were not stimulated by TMA, suggesting that TMA-induced increase in fatty acid transport may be mediated by an increase in FAT/CD36 and/or FATP4 activity and/or fatty acid passive transport. This study demonstrated that TMA increases the intestinal absorption of fatty acids. Future studies are necessary to confirm if this may constitute a novel mechanism that partially explains the existing positive association between the consumption of a diet rich in TMA sources (e.g. red meat) and the increased risk of atherosclerotic diseases.

Elevated plasma intestinal fatty acid binding protein and aberrant lipid metabolism predict post-stroke depression

Post-stroke depression (PSD) is the most common mood disorder caused by stroke. Stroke might bring about increased intestinal permeability accompanied by gut microbiota changes. According to the “gut-brain” axis hypothesis, increased intestinal permeability may contribute to PSD. Therefore, we investigated the association between increased intestinal permeability and the occurrence of PSD. Intestinal fatty acid binding protein (iFABP) is responsible for intestinal fatty acid absorption and transport and is often considered a biomarker of gut hyperpermeability, also known as leaky gut. We enrolled 48 healthy controls (HCs), 48 stroke patients without depression, and 48 PSD patients in this study. Plasma iFABP was measured in the three groups. CRP, LBP, and sCD14 were quantified for bacterial infection assessment. In addition, clinical laboratory indicators of lipid metabolism were assessed. The PSD patients exhibited higher iFABP levels compared with HCs and non-depressed stroke patients. Using OPLS discriminant analysis, four proteins (ApoA1, HDL-C, iFABP, and Lp(a)) were identified as potential biomarkers for distinguishing PSD patients from non-depression stroke patients. Our study discovered that elevated plasma iFABP levels in PSD patients correlated with the degree of depression, along with disturbed lipid metabolism. These findings also suggested the need to consider the role of a leaky gut in depression after stroke.

Relationship between the humoral link of immunity, cytokine regulation with short-chain fatty acids in patients with inflammatory bowel diseases

Background. The pathogenesis of chronic inflammatory bowel disease (IBD) is still not fully clarified. Modern research is aimed at studying the state of humoral immunity, production and intestinal absorption of short-chain fatty acids (SCFA). The purpose was to assess the state of the humoral part of immunity, cytokine regulation and the content of short-chain fatty acids in the feces of patients with IBD. Materials and methods. The study, which was carried out at the Department of Intestinal Diseases of the Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine, involved 34 patients with IBD: groupI— those with ulcerative colitis (UC) (n=25), group II— individuals with Crohn’s disease (n=9). Determination of fecal SCFA, level of CD22+ lymphocytes, immunoglobulins A, M, G, interleukin-10 and TNF-α was determined. Results. There was a decrease in the humoral level of immunity, increase in the content of propionic (C3) acid (p<0.001) and a decrease in acetic (C2) (p<0.001) and butyric (C4) (p<0.001) acids in the coprofiltrate of patients with IBD. The level of TNF-α was significantly higher in patients with mild UC (13.3 times, p<0.05), in patients with moderate UC (17.4 times, p<0.05) and in patients with Severe UC (19.4 times, p <0.05) compared with its level in the control group; it was found that in the group of patients with severe UC there was a significant decrease in the content of butyric acid (C4) in 2.8 times relative to the control group (p<0,01). Conclusions. In our study, a relationship was established between the level of humoral immunity, cytokine regulation and the content of FFA in feces, which may indicate the participation of intestinal metabolites in the activation of human immunity.

Distinct Effects of Short Chain Fatty Acids on Host Energy Balance and Fuel Homeostasis With Focus on Route of Administration and Host Species.

Accumulating evidence implicates gut-microbiota-derived metabolites as important regulators of host energy balance and fuel homeostasis, the underlying mechanisms are currently subject to intense research. In this review, the most important executors, short chain fatty acids, which both directly and indirectly fulfill the interactions between gut microbiota and host will be discussed. Distinct roles of individual short chain fatty acids and the different effects they exert on host metabolism have long been overlooked, which compromises the process of clarifying the sophisticated crosstalk between gut microbiota and its host. Moreover, recent findings suggest that exogenously administered short chain fatty acids affect host metabolism via different mechanisms depending on the routes they enter the host. Although these exogenous routes are often artificial, they may help to comprehend the roles of the short-chain-fatty-acid mechanisms and signaling sites, that would normally occur after intestinal absorption of short chain fatty acids. Cautions should be addressed of generalizing findings, since different results have appeared in different host species, which may imply a host species-specific response to short chain fatty acids.

Dietary supplementation with Korean pine nut oil decreases body fat accumulation and dysregulation of the appetite-suppressing pathway in the hypothalamus of high-fat diet-induced obese mice.

BACKGROUND/OBJECTIVESKorean pine nut oil (PNO) has been reported to suppress appetite by increasing satiety hormone release. However, previous studies have rendered inconsistent results and there is lack of information on whether dietary Korean PNO affects the expression of satiety hormone receptors and hypothalamic neuropeptides. Therefore, our study sought to evaluate the chronic effects of Korean PNO on the long-term regulation of energy balance.MATERIALS/METHODSFive-week-old male C57BL/6 mice were fed with control diets containing 10% kcal fat from Korean PNO or soybean oil (SBO) (PC or SC) or high-fat diets (HFDs) containing 35% kcal fat from lard and 10% kcal fat from Korean PNO or SBO (PHFD or SHFD) for 12 weeks. The expression of gastrointestinal satiety hormone receptors, hypothalamic neuropeptides, and genes related to intestinal lipid absorption and adipose lipid metabolism was then measured.RESULTSThere was no difference in the daily food intake between PNO- and SBO-fed mice; however, the PC and PHFD groups accumulated 30% and 18% less fat compared to SC and SHFD, respectively. Korean PNO-fed mice exhibited higher messenger RNA (mRNA) expression of Ghsr (ghrelin receptor) and Agrp (agouti-related peptide) (P < 0.05), which are expressed when energy consumption is low to induce appetite as well as the appetite-suppressing neuropeptides Pomc and Cartpt (P = 0.079 and 0.056, respectively). Korean PNO downregulated jejunal Cd36 and epididymal Lpl mRNA expressions, which could suppress intestinal fatty acid absorption and fat storage in white adipose tissue. Consistent with these findings, Korean PNO-fed mice had higher levels of fecal non-esterified fatty acid excretion. Korean PNO also tended to downregulate jejunal Apoa4 and upregulate epididymal Adrb3 mRNA levels, suggesting that PNO may decrease chylomicron synthesis and induce lipolysis.CONCLUSIONSIn summary, Korean PNO attenuated body fat accumulation, and appeared to prevent HFD-induced dysregulation of the hypothalamic appetite-suppressing pathway.

Piperine Improves Obesity by Inhibiting Fatty Acid Absorption and Repairing Intestinal Barrier Function

Currently, the weight loss effects of piperine have gained considerable attention; however, the underlying mechanism needs to be comprehensively elucidated. In the present study, we aimed to investigate the relationship between the weight loss effects of piperine and intestinal function. Based on the obtained results, piperine inhibited intestinal fatty acid absorption in both cellular and animal models. The underlying mechanism may be related to the downregulation of fatty acid absorption-related genes, fatty acid-binding protein 2 and cluster of differentiation 36, but not fatty acid transport protein 4. In addition, piperine repaired the tight junction damage induced by obesity by downregulating jejunal tumor necrosis factor-α and reducing lipopolysaccharide-induced damage on intestinal cell proliferation, thus enhancing intestinal barrier function, which is beneficial in reducing chronic inflammation associated with obesity. In conclusion, the anti-obesity effect of piperine is related to the enhancement of intestinal barrier function and inhibition of intestinal fatty acid absorption.

Evaluation of the intestinal microbiota and short-chain fatty acids content in patients with chronic inflammatory bowel diseases

Background. The pathogenesis of chronic inflammatory bowel disease (IBD) is still not fully clarified. It is known that disorders of the intestinal microbiota lead to an increased intestinal permeability, activation of mucous and adaptive immunity, impaired production and intestinal absorption of short-chain fatty acids (SCFA). The ratio of acetic, propionic, butyric acids is an important indicator of the integrity of the intestinal microbial community. Thus, the study of the composition of the intestinal microbiota and the concentrations of fecal SCFA is a very promising approach to broadening the understanding of IBD pathogenesis. The purpose of our study was to determine the features of the production of fecal SCFA and the composition of colon microbiota in patients with IBD. Materials and methods. The study, which was carried out at the Department of Intestinal Diseases of the Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine, involved 74 patients with IBD with an average age of (43.2±1.8) years, who according to nosology were divided into 2 groups: group I— those with ulcerative colitis (UC) (n=66), group II— individuals with Crohn’s disease (CD) (n=8). The diagnoses of CD and UC were established according to generally accepted diagnostic standards in gastroenterology. Determination of fecal SCFA was carried out by chromatographic method with the use of hardware-software complex for medical researches on the basis of the gas chromatographer Chromateс Crystal 5000. The intestinal microflora was evaluated using a microbiological study of the colon content. Results. Patients with IBD had significant changes in the spectrum of SCFA, which were similar in both UC and CD: a decrease in acetic acid in the UC group by 5.7 times, in the CD group by 10.5 times (p&lt;0.05), butyric acid in the UC group by 1.6 times, in the CD group by 1.5 times (p&lt;0.05), and an increase in propionic acid in the UC group by 4 times and in the CD group by 3.3 times (p&lt;0.05) compared with the control group. There was also a significant increase in the anaerobic index in patients with IBD. Microbiological study of feces showed a significant decrease in Lactobacillus, which was observed in all patients with IBD, as well as a decrease in Bifidobacterium in 19.7% of those with UC and in 37.5% with CD. There was a decrease of other representatives of the normal microflora: Enterococci (in 15.2% in the UC group and 25% in the CD group) and Escherichia coli (in 15.2% in the UC group and 12.5% in the CD group). Excessive growth of opportunistic flora was also detected: hemolytic Escherichia coli was increased in 19.7% of patients with UC and in 12.5% of those with CD; Proteus was detected in 12.1% of people with UC and in 37.5% with CD. The excessive growth of Candida was found in 43.9% of patients in the UC group and in 87.5% of individuals with CD. Conclusions. Quantitative and qualitative deviations of the intestinal microbiota, such as a decrease in the number of major symbionts and an increase in the number of opportunistic pathogens, were observed in all examined patients with IBD. The obtained results showed that changes in SCFA concentrations in both nosologies of IBD differed significantly from those in the control group, which in combination with primary genetic defects of the barrier function of the epithelium and its regenerative ability can lead to deterioration in the course and prognosis of IBD. Evaluation of the ratio of SCFA fractions with the calculation of the anaerobic index may be useful for the diagnosis of intestinal dysbiosis in patients with IBD.

Оценка состояния интестинальной микрофлоры и содержания короткоцепочечных жирных кислот копрофильтрата у детей с неалкогольной жировой болезнью печени

Актуальность. Качественные и количественные изменения кишечного микробиома способствуют развитию и прогрессированию неалкогольной жировой болезни печени (НАЖБП). Девиации представительства кишечной микрофлоры ассоциированы с повышением кишечной проницаемости, активацией врожденных и адаптивных иммунных реакций, увеличением продукции и всасывания в кишечнике короткоцепочечных жирных кислот (КЖК). Соотношение уксусной, пропионовой и масляной кислот является важным показателем целостности микробного сообщества кишечника. Таким образом, изучение состава кишечной микробиоты и продукции короткоцепочечных жирных кислот представляет собой перспективное направление, способствующее пониманию механизмов, приводящих к развитию НАЖБП у детей. Цель работы: изучить особенности состояния кишечной микрофлоры и содержания фекальных короткоцепочечных жирных кислот у детей с НАЖБП. Материалы и методы. Комплексное обследование 102 детей было проведено в отделении детской гастроэнтерологии Института гастроэнтерологии Национальной академии медицинских наук Украины. В зависимости от наличия ожирения, данных транзиентной эластографии и уровня аланинаминотрансферазы пациенты были разделены на четыре группы: I группа — дети с простым стеатозом печени (n = 24); II группа — дети с неалкогольным стеатогепатитом (НАСГ) (n = 14); III группа — дети с ожирением без стеатоза (n = 48), IV группа — дети с нормальным весом (n = 16). Хроматографическое исследование КЖК проводилось с помощью газового хроматографа «Хроматек-Кристалл 5000». Идентификация микроорганизмов осуществлялась с использованием микробиологического исследования содержимого толстой кишки. Диагноз НАЖБП подтвержден при помощи аппарата «FibroScan 502 Touch» (Echosens, Франция) с определением контролируемого параметра затухания ультразвука. Результаты. У детей с ожирением (III группа) выявлены значительные изменения в спектре КЖК: увеличение содержания уксусной кислоты в 4,8 раза (р &lt; 0,05), пропионовой кислоты в 1,5 раза (р &lt; 0,001) и масляной кислоты в 1,7 раза в сравнении с контрольной группой. У детей с НАСГ содержание уксусной кислоты в копрофильтрате было увеличено в 2,5 раза, пропионовой и масляной кислот в 1,4 раза по сравнению с контрольной группой (р = 0,1). Также наблюдалось значительное снижение анаэробного индекса у пациентов с НАЖБП. Микробиологическое исследование кала продемонстрировало снижение количества бифидобактерий у 11,8 % пациентов I группы и у 8,3 % III группы; снижение содержания Lactobacillus у 70,6 % детей I группы, у всех детей с НАСГ, у 70,8 % пациентов III группы. Избыточный рост Klebsiella обнаружен у 23,5 % пациентов I группы и у 8,3 % детей III группы. Патогенный стафилококк выявлен у 5,9 % пациентов I группы, у 8,3 % пациентов III группы. Избыточный рост Candida был выявлен у 23,5 % детей I группы, у 14,3 % детей II группы и у 20,8 % детей III группы. Выводы. У детей с НАЖБП и ожирением наблюдаются количественные и качественные изменения кишечной микробиоты в виде уменьшения численности основных симбионтов и увеличения представительства условно-патогенной микро­флоры. Наиболее выраженные изменения спектра фекальных КЖК были обнаружены у детей, страдающих ожирением, что может свидетельствовать о значимости нарушений микро­флоры кишечника на ранних стадиях развития НАЖБП. Определение соотношения фракций фекальных КЖК с вычислением анаэробного индекса может быть полезным для оценки состояния кишечной микрофлоры у детей с НАЖБП.

Attenuation of the Hepatoprotective Effects of Ileal Apical Sodium Dependent Bile Acid Transporter (ASBT) Inhibition in Choline-Deficient L-Amino Acid-Defined (CDAA) Diet-Fed Mice.

Non-alcoholic fatty liver disease (NAFLD) is a major growing worldwide health problem. We previously reported that interruption of the enterohepatic circulation of bile acids using a non-absorbable apical sodium-dependent bile acid transporter inhibitor (ASBTi; SC-435) reduced the development of NAFLD in high fat diet fed mice. However, the ability of ASBTi treatment to impact the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis in a diet-induced mouse model remains untested. In the current study, we assessed whether ASBTi treatment is hepatoprotective in the choline-deficient, L-amino acid-defined (CDAA) diet model of NASH-induced fibrosis.Methods: Male C57Bl/6 mice were fed with: (A) choline-sufficient L-amino acid-defined diet (CSAA) (31 kcal% fat), (B) CSAA diet plus ASBTi (SC-435; 60 ppm), (C) CDAA diet, or (D) CDAA diet plus ASBTi. Body weight and food intake were monitored. After 22 weeks on diet, liver histology, cholesterol and triglyceride levels, and gene expression were measured. Fecal bile acid and fat excretion were measured, and intestinal fat absorption was determined using the sucrose polybehenate method.Results: ASBTi treatment reduced bodyweight gain in mice fed either the CSAA or CDAA diet, and prevented the increase in liver to body weight ratio observed in CDAA-fed mice. ASBTi significantly reduced hepatic total cholesterol levels in both CSAA and CDAA-fed mice. ASBTi-associated significant reductions in hepatic triglyceride levels and histological scoring for NAFLD activity were observed in CSAA but not CDAA-fed mice. These changes correlated with measurements of intestinal fat absorption, which was significantly reduced in ASBTi-treated mice fed the CSAA (85 vs. 94%, P < 0.001) but not CDAA diet (93 vs. 93%). As scored by Ishak staging of Sirius red stained liver sections, no hepatic fibrosis was evident in the CSAA diet mice. The CDAA diet-fed mice developed hepatic fibrosis, which was increased by the ASBTi.Conclusions: ASBT inhibition reduced intestinal fat absorption, bodyweight gain and hepatic steatosis in CSAA diet-fed mice. The effects of the ASBTi on steatosis and fat absorption were attenuated in the context of dietary choline-deficiency. Inhibition of intestinal absorption of fatty acids may be involved in the therapeutic effects of ASBTi treatment.

Emerging Role of Lymphatics in the Regulation of Intestinal Lipid Mobilization.

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 post-assembly 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.

A protective mechanism of probiotic Lactobacillus against hepatic steatosis via reducing host intestinal fatty acid absorption

The gut microbiome has been known to contribute up to ~30% of the energy absorption of the host. Although various beneficial mechanisms of probiotics have been suggested for non-alcoholic fatty liver disease (NAFLD), whether and which probiotics impact the host’s intestinal energy absorption have not yet been quantitatively studied. Here, we suggest a novel mechanism of probiotics against NAFLD, in which Lactobacillus rhamnosus GG, the most common probiotic, shares intestinal fatty acids and prevents the development of diet-induced hepatic steatosis. By using quantitative methods (radioactive tracers and LC–MS) under both in vitro and in vivo conditions, we found that bacteria and hosts competed for fatty acid absorption in the intestine, resulting in decreased weight gain, body fat mass, and hepatic lipid accumulation without differences in calorie intake and excretion in mice fed the probiotic bacteria.

Clostridium ramosum regulates enterochromaffin cell development and serotonin release

Peripheral serotonin (5-hydroxytryptamine: 5-HT) synthesized in the intestine by enterochromaffin cells (ECs), plays an important role in the regulation of peristaltic of the gut, epithelial secretion and promotes the development and maintenance of the enteric neurons. Recent studies showed that the indigenous gut microbiota modulates 5-HT signalling and that ECs use sensory receptors to detect dietary and microbiota-derived signals from the lumen to subsequently transduce the information to the nervous system. We hypothesized that Clostridium ramosum by increasing gut 5-HT availability consequently contributes to high-fat diet-induced obesity. Using germ-free mice and mice monoassociated with C. ramosum, intestinal cell lines and mouse organoids, we demonstrated that bacterial cell components stimulate host 5-HT secretion and program the differentiation of colonic intestinal stem progenitors toward the secretory 5-HT-producing lineage. An elevated 5-HT level regulates the expression of major proteins involved in intestinal fatty acid absorption in vitro, suggesting that the presence of C. ramosum in the gut promotes 5-HT secretion and thereby could facilitates intestinal lipid absorption and the development of obesity.

Mettl3 Deficiency Sustains Long-Chain Fatty Acid Absorption through Suppressing Traf6-Dependent Inflammation Response.

A better understanding of the molecular mechanism of intestinal fatty acid absorption could lead to novel approaches to treatment and prevention of fatty acid-related metabolic diseases. Although it is confirmed that absorption of long-chain fatty acids (LCFAs) decreases during the pathological processes, the genetic basis and molecular mechanisms remain largely unknown. N 6-methyladenosine (m6A) is the most prevalent internal modification on eukaryotic mRNA. Recently, m6A has been found to play important roles in inflammation and antiviral responses. In this study, we show that deficiency of Mettl3, the core methyltransferase of m6A, exerts antimalabsorption of LCFA activity in vitro through inhibiting the inflammation response mediated by LPS. To substantiate this finding further, we found the levels of triglycerides were also sustained in cells with depleted Mettl3, which were cultured in Transwell to polarize with villus formation to simulate the situation in vivo. Mechanistically, depletion of Mettl3 decreases the m6A level of Traf6 mRNA, thereby its transcripts are entrapped in the nucleus, followed by the decreased expression of Traf6, leading to the suppression of NF-κB and MAPK signaling pathway. Thus, the inflammation response was suppressed, resulting in the sustained absorption of LCFA. Moreover, we found that ectopic expression of Traf6 largely abolishes the sustained absorption LCFA in Mettl3 depletion cells. Collectively, silencing Mettl3 could sustain LCFA absorption through blocking the TRAF6-dependent inflammation response. Our work uncovers a critical function of m6A methylation and provides insight into critical roles of Mettl3 in LCFA absorption and inflammatory disease.

Niacin fine-tunes energy homeostasis through canonical GPR109A signaling.

The incidence of overweight and obesity has become a global public health problem, constituting a major risk factor for numerous comorbidities. Despite tremendous efforts, effective pharmacological agents for the treatment of obesity are still limited. Here, we showed that in contrast to lactate receptor GPR81, niacin receptor GPR109A-deficient mice had progressive weight gain and hepatic fat accumulation. Using high-fat diet-induced mouse model of obesity, we demonstrated that niacin treatment apparently protected against obesity without affecting food intake in wild-type mice but not in GPR109A-deficient mice. Further investigation showed that niacin treatment led to a remarkable inhibition of hepatic de novo lipogenesis. Additionally, we demonstrated that niacin treatment triggered brown adipose tissue and/or white adipose tissue thermogenic activity via activation of GPR109A. Moreover, we observed that mice exposed to niacin exhibited a dramatic decrease in intestinal absorption of sterols and fatty acids. Taken together, our findings demonstrate that acting on GPR109A, niacin shows the potential to maintain energy homeostasis through multipathways, representing a potential approach to the treatment of obesity, diabetes and cardiovascular disease.-Ye, L., Cao, Z., Lai, X., Wang, W., Guo, Z., Yan, L., Wang, Y., Shi, Y., Zhou, N. Niacin fine-tunes energy homeostasis through canonical GPR109A signaling.

Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells.

The intestinal absorption of fatty acids, glucose and fructose is part of the basic requirements for the provision of energy in the body. High access of saturated long-chain fatty acids (LCFA), glucose and fructose can facilitate the development of metabolic diseases, particularly the metabolic syndrome and type-2 diabetes mellitus (T2DM). Research has been done to find substances which decelerate or inhibit intestinal resorption of these specific food components. Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2, FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant extracts and by pure substances. The largest part of active components in plant extracts belongs to the group of polyphenols. This review summarizes the knowledge about binding sites of named transporters and lists the plant extracts which were tested in Caco-2 cells regarding uptake inhibition.

Molecular mechanisms of long-chain fatty acids absorption

The article presents about the role of several lipid-binding proteins expressed by the small intestine brush border membrane in the main steps of intestinal absorption of long-chain fatty acids and about changes in lipid profile caused by failed absorbtion. The system literature search is performed on Scopus databases, Web of Science, MedLine.

Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice.

Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism by which quercetin lowers plasma TG levels in diet-induced obesity. C57Bl/6J mice received a high-fat diet (45% of calories derived from fat) with or without quercetin (0.1% w/w) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%, p < 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver Apob expression (−13%, p < 0.05), which suggests decreased very-low density lipoprotein-TG production. Interestingly, quercetin also markedly increased the uptake of [3H]oleate, which was derived from glycerol tri[3H]oleate-labeled lipoprotein-like particles by subcutaneous white adipose tissue (sWAT, +60%, p < 0.05). Furthermore, quercetin also markedly increased mRNA expression of Ucp1 (+229%, p < 0.05) and Elovl3 (+138%, p < 0.05), specifically in sWAT. Accordingly, only quercetin-treated animals showed uncoupling protein-1 protein-positive cells in sWAT, which is fully compatible with increased browning. Taken together, the TG-lowering effect of quercetin may, at least in part, be due to increased TG-derived FA uptake by sWAT as a consequence of browning.