Improving the accuracy of the SRK/T formula in Chinese with implanting less than 10 D IOL calculated by the SRK/T formula: the SRK/T-Li formula.

PURPOSE: To explore the accuracy of the improved SRK/T-Li formula in eyes following implantation of intraocular lens (IOL) of less than 10 D as calculated by using the SRK/T formula in Chinese. METHODS: A total of 489 eyes from 489 patients with cataracts were included in this study. These patients were divided into a training set (271 patients) and a testing set (218 patients). The IOL power calculated by using SRK/T was less than 10 D. We evaluated the accuracy of the modified SRK/T-Li formula (P = PSRK/T × 0.8 + 2 (P = implanted IOL power; PSRK/T = IOL power calculated by SRK/T)). We evaluated the mean absolute error (MAE), percentage of prediction error (PE) within ± 0.25, ± 0.50, and ± 1.00 D, and the percentage of postoperative hyperopia. RESULTS: The MAE values in order of lowest to highest were as follows: 0.412 D (SRK/T-Li), 0.414 D (Barrett Universal II, (BUII)), 0.814 D (SRK/T), and 1.039 D (Holladay 1). The percentage of PE within ± 0.25 D, ± 0.50 D, and ± 1.00 D was 38.99%, 69.27% and 92.66% (BUII), 40.83%, 69.27% and 94.04% (SRK/T-Li), 20.64%, 41.28% and 71.56% (SRK/T), and 7.34%, 16.51% and 53.21% (Holladay 1), respectively. SRK/T-Li had the smallest postoperative hyperopic shift. CONCLUSIONS: For Chinese patients with an IOL power of less than 10 D as calculated by using the SRK/T, the SRK/T-Li has good accuracy and is the best choice to reduce postoperative hyperopic shift.

Refractive outcomes of toric intra-ocular lens implantation in cases of high posterior corneal astigmatism.

Purpose: To evaluate whether the toric intra-ocular lens (IOL) power calculation based on total corneal astigmatism (TCA) in eyes with high posterior corneal astigmatism (PCA) could result in a systematic over-correction or under-correction after operation. Methods: The present study included a mono-centric retrospective study design. The data were collected from 62 consecutive eyes during uncomplicated cataract surgery by a single surgeon with a measured PCA of 0.50 diopters (D) or higher. Toric IOL calculations were made using TCA measurements. The eyes were grouped as either "with-the-rule" (WTR) or "against-the-rule" (ATR) on the basis of the steep anterior corneal meridian. The post-operative refractive astigmatic prediction error was analyzed 1 month post-operatively using the vector analysis by the Alpins method and double-angle plots method. Results: The correction indexes were 1.14 ± 0.29 in the ATR eyes and 1.25 ± 0.18 for the WTR eyes, indicating a tendency toward over-correction. The mean over-correction was 0.22 ± 0.52D in the ATR group and 0.65 ± 0.60D in the WTR group. The magnitude of error (ME) values were significantly different from the ideal value of zero in both groups (ATR: P = 0.03; WTR: P = 0.00). No significant difference in mean absolute error (MAE) in predicted residual astigmatism was found between ATR and WTR groups (0.61 ± 0.42 D versus 0.64 ± 0.39 D; P = 0.54). The ATR group yielded better results, with 48% <0.50D prediction error in the main analysis. Conclusions: The results suggested that in cases of high PCA, the toric IOL calculation, which was performed using TCA, may cause a potential over-correction in the ATR and WTR eyes. For ATR eyes, over-correction led to slight disruption of post-operative visual quality because of the "with-the-rule" residual astigmatism after operation. Therefore, we suggested using TCA for toric IOL calculation in ATR eyes.

Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1.

Two common features of dietary polyphenols have hampered our mechanistic understanding of their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression of jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1-/- mice on HFD-challenge exhibit improved lipid homeostasis but show virtually no further response to REV-I. SR-B1 expression in Caco-2 cells cannot be repressed by pure resveratrol compound while fecal-microbiota transplantation from mice on REV-I suppresses jejunal SR-B1 in recipient mice. REV-I reduces fecal levels of bile acids and activity of fecal bile-salt hydrolase. In Caco-2 cells, chenodeoxycholic acid treatment stimulates both FXR and SR-B1. We conclude that gut microbiome is the primary target of REV-I, and REV-I improves lipid homeostasis at least partially via attenuating FXR-stimulated gut SR-B1 elevation.

Short-term semaglutide treatment improves FGF21 responsiveness in primary hepatocytes isolated from high fat diet challenged mice.

Metabolic functions of GLP-1 and its analogues have been extensively investigated. In addition to acting as an incretin and reducing body weight, we and others have suggested the existence of GLP-1/fibroblast growth factor 21 (FGF21) axis in which liver mediates certain functions of GLP-1 receptor agonists. In a more recent study, we found with surprise that four-week treatment with liraglutide but not semaglutide stimulated hepatic FGF21 expression in HFD-challenged mice. We wondered whether semaglutide can also improve FGF21 sensitivity or responsiveness and hence triggers the feedback loop in attenuating its stimulation on hepatic FGF21 expression after a long-term treatment. Here, we assessed effect of daily semaglutide treatment in HFD-fed mice for 7 days. HFD challenge attenuated effect of FGF21 treatment on its downstream events in mouse primary hepatocytes, which can be restored by 7-day semaglutide treatment. In mouse liver, 7-day semaglutide treatment stimulated FGF21 as well as genes that encode its receptor (FGFR1) and the obligatory co-receptor (KLB), and a battery of genes that are involved in lipid homeostasis. In epididymal fat tissue, expressions of a battery genes including Klb affected by HFD challenge were reversed by 7-day semaglutide treatment. We suggest that semaglutide treatment improves FGF21 sensitivity which is attenuated by HFD challenge.

An evaluation of the accuracy of toric intraocular lens power calculation based on measured total corneal refractive power.

Purpose: To evaluate a method using measured values of total corneal refractive power (TCRP) for a manufacturer's online calculator by comparing it with the Barrett toric calculator (BTC) and Kane toric calculator (KTC) combined with simulated keratometry values (SimK). Methods: This was a retrospective case series. Patient records were reviewed to identify the patients who had biometry with the IOL Master 700 and Pentacam recorded before toric IOL implantation and refractive follow-up data after implantation. The predicted error in residual astigmatism was calculated by vector analysis according to the calculation methods and the measurements used. Results: A total of 70 eyes of 56 patients were included. The mean absolute astigmatism prediction errors were 0.6 ± 0.32, 0.59 ± 0.35, and 0.61 ± 0.35 D for the ATCTCRP, BTCSimK, and KTCSimK calculators, respectively (P = 0.934), and the centroid of the prediction errors were 0.3 D @ 178°, 0.11 D @ 102°, and 0.09 D @ 147°, respectively (P = 0.23). In the with-the-rule subgroup, the centroid of the prediction error was 0.34 D @ 176° for ATCTCRP and was the highest among the three calculation methods (P = 0.046). Conclusion: The ATCTCRP, BTCSimK, and KTCSimK calculators had similar performance with regards to their astigmatism prediction accuracy. The ATCTCRP calculator combined with 4.0-mm apex/ring readings of TCRP was slightly intended to result in against-the-rule residual astigmatism.

The anti-inflammatory feature of glucagon-like peptide-1 and its based diabetes drugs-Therapeutic potential exploration in lung injury.

Since 2005, GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) have been developed as therapeutic agents for type 2 diabetes (T2D). GLP-1R is not only expressed in pancreatic islets but also other organs, especially the lung. However, controversy on extra-pancreatic GLP-1R expression still needs to be further resolved, utilizing different tools including the use of more reliable GLP-1R antibodies in immune-staining and co-immune-staining. Extra-pancreatic expression of GLP-1R has triggered extensive investigations on extra-pancreatic functions of GLP-1RAs, aiming to repurpose them into therapeutic agents for other disorders. Extensive studies have demonstrated promising anti-inflammatory features of GLP-1RAs. Whether those features are directly mediated by GLP-1R expressed in immune cells also remains controversial. Following a brief review on GLP-1 as an incretin hormone and the development of GLP-1RAs as therapeutic agents for T2D, we have summarized our current understanding of the anti-inflammatory features of GLP-1RAs and commented on the controversy on extra-pancreatic GLP-1R expression. The main part of this review is a literature discussion on GLP-1RA utilization in animal models with chronic airway diseases and acute lung injuries, including studies on the combined use of mesenchymal stem cell (MSC) based therapy. This is followed by a brief summary.

Liraglutide stimulates the ß-catenin signaling cascade in mouse epididymal fat tissue.

Although canonical Wnt signaling pathway activation was shown to negatively regulate adipogenesis, recent investigations suggest that Wnt pathway effectors TCF7L2 and ß-catenin (ß-cat) in adipose tissues are also involved in energy homeostasis during adulthood. In assessing the metabolic beneficial effect of GLP-1-based diabetes drugs in high-fat diet (HFD)-challenged mice, we observed that liraglutide treatment affected the expression of a battery of adipose tissue-specific genes, including those that encode adiponectin and leptin, mainly in epididymal white adipose tissue (eWAT). Fourteen-week HFD challenge repressed TCF7L2 and ß-cat S675 phosphorylation in eWAT, while such repression was reversed by liraglutide treatment (150 µg/kg body weight daily) during weeks 10-14. In Glp1r-/-mice, liraglutide failed in stimulating TCF7L2 or ß-cat in eWAT. We detected Glp1r expression in mouse eWAT and its level is enriched in its stromal vascular fraction (SVF). Mouse eWAT-SVF showed reduced expression of Tcf7l2 and its Tcf7l2 level could not be stimulated by liraglutide treatment; while following adipogenic differentiation, rat eWAT-SVF showed elevated Tcf7l2 expression. Direct in vitro liraglutide treatment in eWAT-SVF stimulated CREB S133, ß-cat S675 phosphorylation, and cellular cAMP level. Thus, cAMP/ß-cat signaling cascade can be stimulated by liraglutide in eWAT via GLP-1R expressed in eWAT-SVF.

Hepatic hormone FGF21 and its analogues in clinical trials.

Fibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and ß-klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD). Here we have reviewed FGF21 gene and protein structures, its expression pattern, cellular signaling cascades that mediate FGF21 production and function. We have then summarized the six clinical trials utilizing four FGF21 analogues. Finally, two recent literatures on the development of GLP-1 and FGF21 dual agonists were presented briefly.

Comparison of Beneficial Metabolic Effects of Liraglutide and Semaglutide in Male C57BL/6J Mice.

OBJECTIVES: Semaglutide and liraglutide are glucagon-like peptide-1 (GLP-1)-based diabetes drugs. Semaglutide possesses a longer half-life. Utilizing relatively lower doses, we compared the beneficial metabolic effects of these 2 drugs in mice fed a high-fat diet (HFD), aiming to deepen our mechanistic understanding on their energy homeostatic functions. METHODS: Male C57BL/6J mice were fed an HFD for 10 weeks, followed by daily phosphate-buffered saline (PBS, as control); liraglutide (150 µg/kg body weight); or semaglutide (12 µg/kg body weight, low dose [LD]; or 60 µg/kg body weight, high dose [HD]) injection for 4 weeks. Metabolic tolerance and other tests were conducted within the 4-week period. Expression of metabolism-related genes, including Fgf21 in the liver and adipose tissues, was assessed after mice were euthanized. RESULTS: HFD-induced body weight gain, increasing inguinal fat tissue mass, glucose defects and insulin intolerance were effectively and comparably attenuated in the 3 experimental groups. HD semaglutide showed an even better effect on attenuating hyperleptinemia. Liraglutide but not semaglutide treatment enhanced hepatic fibroblast growth factor 21 (FGF21) protein level. All 3 experimental groups showed elevated expression of genes that encode pyruvate dehydrogenase kinase 4 and enoyl-CoA hydratase and 3-hydroxyacyl-coenzyme A dehydrogenase, associated with reduced plasma triglyceride levels. Finally, the plasma "GLP-1" level in HD semaglutide-treated mice was 14-fold higher than in HFD-fed control mice. CONCLUSIONS: Liraglutide, but not semaglutide, increased hepatic FGF21 protein level, whereas semaglutide had a greater effect on attenuating hyperleptinemia. Thus, these 2 GLP-1-based diabetes drugs may target metabolic organs, including liver and adipose tissue, with differing levels of efficacy.

Fibroblast growth factor 21 and dietary interventions: what we know and what we need to know next.

Dietary interventions include the change of dietary styles, such as fasting and dietary or nutrient restrictions; or the addition of plant-derived compounds (such as polyphenols known as curcumin, resveratrol, or anthocyanin, or other nutraceuticals) into the diet. During the past a few decades, large number of studies have demonstrated therapeutic activities of these dietary interventions on metabolic and other diseases in human subjects or various animal models. Mechanisms underlying those versatile therapeutic activities, however, remain largely unclear. Interestingly, recent studies have shown that fibroblast growth factor 21 (FGF21), a liver-derived hormone or hepatokine, mediates metabolic beneficial effects of certain dietary polyphenols as well as protein restriction. Here I have briefly summarized functions of FGF21, highlighted related dietary interventions, and presented literature discussions on role of FGF21 in mediating function of dietary polyphenol intervention and protein restriction. This is followed by presenting my perspective view, with the involvement of gut microbiota. It is anticipated that further breakthroughs in this field in the near future will facilitate conceptual merge of classical medicine and modern medicine.

Estrogen-Wnt signaling cascade regulates expression of hepatic fibroblast growth factor 21.

We have generated the transgenic mouse line LTCFDN in which dominant negative TCF7L2 (TCF7L2DN) is specifically expressed in the liver during adulthood. Male but not female LTCFDN mice showed elevated hepatic and plasma triglyceride (TG) levels, indicating the existence of estrogen-ß-cat/TCF signaling cascade that regulates hepatic lipid homeostasis. We show here that hepatic fibroblast growth factor 21 (FGF21) expression was reduced in male but not in female LTCFDN mice. The reduction was not associated with altered hepatic expression of peroxisome proliferator-activated receptor α (PPARα). In mouse primary hepatocytes (MPH), Wnt-3a treatment increased FGF21 expression in the presence of PPARα inhibitor. Results from our luciferase-reporter assay and chromatin immunoprecipitation suggest that evolutionarily conserved TCF binding motifs (TCFBs) on Fgf21 promoter mediate Wnt-3a-induced Fgf21 transactivation. Female mice showed reduced hepatic FGF21 production and circulating FGF21 level following ovariectomy (OVX), associated with reduced hepatic TCF expression and ß-catenin S675 phosphorylation. Finally, in MPH, estradiol (E2) treatment enhanced FGF21 expression, as well as binding of TCF7L2 and ribonucleic acid (RNA) polymerase II to the Fgf21 promoter; and the enhancement can be attenuated by the G-protein-coupled estrogen receptor 1 (GPER) antagonist G15. Our observations hence indicate that hepatic FGF21 is among the effectors of the newly recognized E2-ß-cat/TCF signaling cascade.NEW & NOTEWORTHY FGF21 is mainly produced in the liver. Therapeutic effect of FGF21 analogues has been demonstrated in clinical trials on reducing hyperlipidemia. We show here that Fgf21 transcription is positively regulated by Wnt pathway effector ß-cat/TCF. Importantly, hepatic ß-cat/TCF activity can be regulated by the female hormone estradiol, involving GPER. The investigation enriched our understanding on hepatic FGF21 hormone production, and expanded our view on metabolic functions of the Wnt pathway in the liver.

Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy.

S-adenosylhomocysteine (SAH) is hydrolyzed by SAH hydrolase (SAHH) to homocysteine and adenosine. Increased plasma SAH levels were associated with disturbed renal function in patients with diabetes. However, the role and mechanism of SAHH in diabetic nephropathy is still unknown. In the present study, we found that inhibition of SAHH by using its inhibitor adenosine dialdehyde (ADA) accumulates intracellular or plasma SAH levels and increases high glucose-induced podocyte injury and aggravates STZ-induced diabetic nephropathy, which is associated with Nod-like receptor protein 3 (NLRP3) inflammasome activation. Inhibition or knockout of NLRP3 attenuates SAHH inhibition-aggravated podocyte injury and diabetic nephropathy. Additionally, SAHH inhibition increases thioredoxin-interacting protein (TXNIP)-mediated oxidative stress and NLRP3 inflammasome activation, but these effects were not observed in TXNIP knockout mice. Mechanistically, SAHH inhibition increased TXNIP by inhibiting histone methyltransferase enhancer of zeste homolog 2 (EZH2) and reduced trimethylation of histone H3 lysine 27 and its enrichment at promoter of early growth response 1 (EGR1). Moreover, EGR1 is activated and enriched at promoters of TXNIP by SAHH inhibition and is essential for SAHH inhibition-induced TXNIP expression. Inhibition of EGR1 protected against SAHH inhibition-induced NLRP3 inflammasome activation and oxidative stress and diabetic nephropathy. Finally, the harmful effects of SAHH inhibition on inflammation and oxidative stress and diabetic nephropathy were also observed in heterozygote SAHH knockout mice. These findings suggest that EZH2/EGR1/TXNIP/NLRP3 signaling cascade contributes to SAHH inhibition-aggravated diabetic nephropathy. Our study firstly provides a novel insight into the role and mechanism of SAHH inhibition in diabetic nephropathy.

Hepatic Fibroblast Growth Factor 21 Is Involved in Mediating Functions of Liraglutide in Mice With Dietary Challenge.

BACKGROUND AND AIMS: Several studies have shown that expression of hepatic fibroblast growth factor 21 (FGF21) can be stimulated by glucagon-like peptide 1 (GLP-1)-based diabetes drugs. As GLP-1 receptor (GLP-1R) is unlikely to be expressed in hepatocytes, we aimed to compare such stimulation in mice and in mouse hepatocytes, determine the involvement of GLP-1R, and clarify whether FGF21 mediates certain functions of the GLP-1R agonist liraglutide. APPROACH AND RESULTS: Liver FGF21 expression was assessed in mice receiving a daily liraglutide injection for 3 days or in mouse primary hepatocytes (MPHs) undergoing direct liraglutide treatment. The effects of liraglutide on metabolic improvement and FGF21 expression were then assessed in high-fat diet (HFD)-fed mice and compared with the effects of the dipeptidyl-peptidase 4 inhibitor sitagliptin. Animal studies were also performed in Glp1r-/- mice and liver-specific FGF21-knockout (lFgf21-KO) mice. In wild-type mouse liver that underwent RNA sequencing and quantitative reverse-transcription PCR, we observed liraglutide-stimulated hepatic Fgf21 expression and a lack of Glp1r expression. In MPHs, liraglutide did not stimulate Fgf21. In mice with HFD-induced obesity, liraglutide or sitagliptin treatment reduced plasma triglyceride levels, whereas their effect on reducing body-weight gain was different. Importantly, increased hepatic FGF21 expression was observed in liraglutide-treated mice but was not observed in sitagliptin-treated mice. In HFD-fed Glp1r-/- mice, liraglutide showed no beneficial effects and could not stimulate Fgf21 expression. In lFgf21-KO mice undergoing dietary challenge, the body-weight-gain attenuation and lipid homeostatic effects of liraglutide were lost or significantly reduced. CONCLUSIONS: We suggest that liraglutide-stimulated hepatic Fgf21 expression may require GLP-1R to be expressed in extrahepatic organs. Importantly, we revealed that hepatic FGF21 is required for liraglutide to lower body weight and improve hepatic lipid homeostasis. These observations advanced our mechanistic understanding of the function of GLP-1-based drugs in NAFLD.

Friend or foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a pandemic since WHO made the statement on March 11, 2020. The infection is causing a high mortality in old people, especially those with obesity, type 2 diabetes (T2D) or cardiovascular diseases (CVD). Extra cautions are needed in the treatment of those patients. The CVD drugs ACEIs and ARBs, as well as the T2D drugs GLP-1R agonists, were shown to activate angiotensin-converting enzyme 2 (ACE2) expression in experimental animals. Elevated ACE2 expression may accelerate virus entrance into the host cells during the infection for its replication. However, expression of the soluble ACE2, may neutralize the virus to limit the infection and replication. Given that obese, diabetes and CVD patients often take those medicines in the treatment and prevention of blood pressure and glucose elevation, it remains to be determined whether those medicines represent friend or foe in the treatment of COVID-19. We suggest that retrospective studies should be conducted to determine the exact impact of those medicines in obese, diabetic, or CVD patients who had COVID-19. Results obtained will provide guidance whether those drugs can be utilized in COVID-19 patients with obesity, diabetic, or CVD.

Combined use of GABA and sitagliptin promotes human ß-cell proliferation and reduces apoptosis.

γ-Aminobutyric acid (GABA) and glucagon-like peptide-1 receptor agonist (GLP-1RA) improve rodent ß-cell survival and function. In human ß-cells, GABA exerts stimulatory effects on proliferation and anti-apoptotic effects, whereas GLP-1RA drugs have only limited effects on proliferation. We previously demonstrated that GABA and sitagliptin (Sita), a dipeptidyl peptidase-4 inhibitor which increases endogenous GLP-1 levels, mediated a synergistic ß-cell protective effect in mice islets. However, it remains unclear whether this combination has similar effects on human ß-cell. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-gamma mice with streptozotocin-induced diabetes, and then treated them with GABA, Sita, or both. The oral administration of either GABA or Sita ameliorated blood glucose levels, increased transplanted human ß-cell counts and plasma human insulin levels. Importantly, the combined administration of the drugs generated significantly superior results in all these responses, as compared to the monotherapy with either one of them. The proliferation and/or regeneration, improved by the combination, were demonstrated by increased Ki67+, PDX-1+, or Nkx6.1+ ß-cell numbers. Protection against apoptosis was also significantly improved by the drug combination. The expression level of α-Klotho, a protein with protective and stimulatory effects on ß cells, was also augmented. Our study indicates that combined use of GABA and Sita produced greater therapeutic benefits, which are likely due to an enhancement of ß-cell proliferation and a decrease in apoptosis.

Current understanding and controversies on the clinical implications of fibroblast growth factor 21.

Metabolic functions of the hepatic hormone fibroblast growth factor 21 (FGF21) have been recognized for more than a decade in studying the responses of human subjects and rodent models to nutritional stresses such as fasting, high-fat diet or ketogenic diet consumption, and ethanol intake. Our interest in the beneficial metabolic effects of FGF21 has risen due to its potential ability to serve as a therapeutic agent for various metabolic disorders, including type 2 diabetes, obesity, and fatty liver diseases, as well as its potential to act as a diagnostic or prognostic biomarker for metabolic and other disorders. Here, we briefly review the FGF21 gene and protein structures, its expression pattern, and cellular signaling cascades that mediate FGF21 production and function. We mainly focus on discussing experimental and clinical literature pertaining to FGF21 as a therapeutic agent. Furthermore, we present several lines of investigation, including a few studies conducted by our team, suggesting that FGF21 expression and function can be regulated by dietary polyphenol interventions. Finally, we discuss the literature debating FGF21 as a potential biomarker in various disorders.

Glucagon-like peptide-1 receptor mediates the beneficial effect of liraglutide in an acute lung injury mouse model involving the thioredoxin-interacting protein.

Repurposing clinically used drugs is among the important strategies in drug discovery. Glucagon-like peptide-1 (GLP-1) and its diabetes-based drugs, such as liraglutide, possess a spectrum of extra-pancreatic functions, while GLP-1 receptor (GLP-1R) is most abundantly expressed in the lung. Recent studies have suggested that GLP-1-based drugs exert beneficial effects in chronic, as well as acute, lung injury rodent models. Here, we show that liraglutide pretreatment reduced LPS induced acute lung injury in mice. It significantly reduced lung injury score, wet/dry lung weight ratio, bronchoalveolar lavage fluid immune cell count and protein concentration, and cell apoptosis in the lung, and it was associated with reduced lung inflammatory cytokine and chemokine gene expression. Importantly, these effects were virtually absent in GLP-1R-/- mice. A well-known function of GLP-1 and GLP-based drugs in pancreatic ß-cells is the attenuation of high-glucose stimulated expression of thioredoxin-interacting protein (TxNIP), a key component of inflammasome. LPS-challenged lungs showed elevated TxNIP mRNA and protein expression, which was attenuated by liraglutide treatment in a GLP-1R-dependent manner. Hence, our observations suggest that GLP-1R is essential in mediating beneficial effects of liraglutide in acute lung injury, with the inflammasome component TxNIP as a potential target.