Anti-tumoral activities of dioncoquinones B and C and related naphthoquinones gained from total synthesis or isolation from plants

Dioncoquinones belong to a family of natural naphthoquinone products of interest due to their promising anti-tumoral and anti-infective activities. In particular, dioncoquinones A (5) and B (6) have been shown to be highly active against Leishmania major and multiple myeloma cells without any significant toxicity toward normal blood cells. Their effective concentrations against multiple myeloma cell lines were similar to those of melphalan, a well known DNA-alkylating agent used in a standard therapy against B cell lymphoma and multiple myeloma. We report on the first total synthesis of the highly oxygenated anti-tumoral agent dioncoquinone B (6) and the isolation of its new, even higher-oxygenated analogs, dioncoquinones C (7), D (8), and E (9), from cell cultures of Triphyophyllum peltatum. In addition, several derivatives of these compounds were synthesized, including dioncoquinone C (7), and a small library of naphthoquinones was created. Furthermore, the first structure-activity relationship (SAR) study on this class of compounds was conducted, showing that each of the three hydroxy groups, at C-3, C-5, and C-6, is required for improved anti-tumoral activities and decreased cytotoxicities.     

Solvent-free, microwave assisted Knoevenagel condensation of novel 2,5-disubstituted indole analogues and their biological evaluation

A rapid, efficient and environmental benign methodology for the preparation of 2,5-disubstituted indole analogues is developed. 2,5-Disubstituted indole-3-carboxaldehydes (1a–c) undergo Knoevenagel condensation with barbiturates (2 & 4), thiazolidine-2,4-dione (6) and 3-methyl-1H-pyrazol-5(4H)-one (8) in solvent-free, NH₄OAc catalyzed, microwave assisted reaction. Structures of the products thus obtained were confirmed by their m.p, Elemental analysis, IR, ¹H NMR, ¹³C NMR and Mass spectral data. The in vitro antioxidant and cytotoxic activities against three tumor cell lines were evaluated and discussed in terms of their structural differences. Among the screened compounds 9b, 9c, 7b and 5b exhibited excellent antioxidant activity. Compounds 9b, 9c and 7b have shown strong cytotoxicity among the compounds tested.     

Synthesis and antifungal activity of 2/3-arylthio- and 2,3-bis(arylthio)-5-hydroxy-/5-methoxy-1,4-naphthoquinones

2/3-Arylthio- and 2,3-bis(arylthio)-5-hydroxy-/5-methoxy-1,4-naphthoquinones 5-9 were synthesized and tested for in vitro antifungal activity against Candida species and Aspergillus niger. The synthesized compounds 5-9 generally showed good activities against Candida albicans and C. tropicalis. The results suggest that the 1,4-naphthoquinones 5-9 would be potent antifungal agents.     

Diastereoselective synthesis and bioactivity of long-chain anti-2-amino-3-alkanols

An improved four-step approach for the stereoselective synthesis of long-chain anti-2-amino-3-alkanols is described. Using this method, the syntheses of antiproliferative (antitumoral) compounds, spisulosine (ES-285, 2), clavaminols A and B (3 and 4), the deacetylated products of clavaminols H and N (7 and 8), as well as (2S,3R)-2-aminododecan-3-ol (9) and xestoaminol C (10), have been achieved in excellent diastereoselectivities. In vitro study showed that these compounds induced cell death and dose-dependently inhibited cell proliferation in human glioblastoma cell line SHG-44, indicating the anti-tumor property of this series of compounds.     

Synthesis, characterization and pharmacological activity of 4-{[1-substituted aminomethyl-4-arylideneamino-5-sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-2H-1,4-benzothiazin-3(4H)-ones

A new series of Schiff and Mannich bases derivatives (6) of 4-[(4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl)methyl]-2H-1,4-benzothiazin-3(4H)-one (4), derived from (3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)acetic acid (3) were synthesized. The structures of all newly synthesized compounds were elucidated by elemental analysis, IR, ¹H NMR and mass spectral data. Synthesized compounds were evaluated for their anti-inflammatory and analgesic activity. Among the tested compounds, the (3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)acetic acid (3) possess analgesic activity comparable to that of pentazocine; activity decreased on derivatization of the carboxylic acid group. However the anti-inflammatory activity of (3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)acetic acid (3) increased by derivatization of the carboxylic acid group and some of the compounds showed anti-inflammatory activity comparable to that of indomethacin.     

Relationship Between Protein Intake in Each Traditional Meal and Physical Activity: Cross-sectional Study

BackgroundProtein intake plays an important role in the synthesis and maintenance of skeletal muscles for the prevention of health risks. It is also widely known that physical activity influences muscle function. However, no large-scale studies have examined the relationship between daily dietary habits, especially the timing of protein intake, and daily physical activity.ObjectiveThe purpose of this cross-sectional study was to investigate how protein intake and composition (involving the 3 major nutrients protein, fat, and carbohydrate) in the 3 traditional meals (breakfast, lunch, and dinner) are associated with physical activity.MethodsUsing daily dietary data accumulated in the smartphone food log app “Asken” and a web-based cross-sectional survey involving Asken users (N=8458), we analyzed nutrient intake and composition, as well as daily activity levels. As very few individuals skipped breakfast (1102/19,319 responses, 5.7%), we analyzed data for 3 meals per day.ResultsSpearman rank correlation analysis revealed that breakfast and lunch protein intakes had higher positive correlations with daily physical activity among the 3 major macronutrients (P<.001). These findings were confirmed by multivariate logistic regression analysis with confounding factors. Moreover, participants with higher protein intake and composition at breakfast or lunch tended to exhibit significantly greater physical activity than those with higher protein intake at dinner (P<.001).ConclusionsAmong the 3 macronutrients, protein intake during breakfast and lunch was closely associated with daily physical activity.     

Biological monitoring of occupational exposure to cyclohexane by urinary 1,2- and 1,4-cyclohexanediol determination

Objectives: This article reports the results obtained with the biological and environmental monitoring of occupational exposure to cyclohexane using 1,2-cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL in urine suggested by a physiologically based pharmacokinetic (PBPK) model was compared with the results obtained in workers. Methods: Individual exposure to cyclohexane was measured in 156 workers employed in shoe and leather factories. The biological monitoring of cyclohexane exposure was done by measurement of 1,2-DIOL and 1,4-DIOL in urine collected on different days of the working week. In all, 29 workers provided urine samples on Monday (before and after the work shift) and 47 workers provided biological samples on Thursday at the end of the shift and on Friday morning. Another 86 workers provided biological samples at the end of the work shift only on Monday or Thursday. Results: Individual exposure to cyclohexane ranged from 7 to 617 mg/m³ (geometric mean value 60 mg/m³). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2, and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically significant correlation was found between environmental exposure to cyclohexane and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday and Friday showed only a poor correlation to exposure with a wide scatter. Both metabolites have a urinary half-life of close to 18 h and accumulate during the working week. Conclusions: Comparison between data obtained from a PBPK model and those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary metabolites suitable for the biological monitoring of industrial exposure to cyclohexane. Received: 17 June 1998 / Accepted: 23 September 1998     

Anti-Toxoplasma Activity of 2-(Naphthalene-2-γlthiol)-1H Indole

Background:

This study was undertaken to evaluate the viability, infectivity and immunity of Toxoplasma gondii tachyzoites exposed to 2-(naphthalene-2-ylthio)-1H-indole.

Methods:

Tachyzoites of RH strain were incubated in various concentrations of 2-(naphthalene-2-ylthio)-1H-indole (25–800 μM) for 1.5 hours. Then, they were stained by PI and analyzed by Fluorescence-activated cell sorting (FACS). To evaluate the infectivity, the tachyzoites exposed to the different concentrations of the compound were inoculated to 10 BALB/c mice groups. For Control, parasites exposed to DMSO (0.2% v/v) were also intraperitoneally inoculated into two groups of mice. The immunity of the exposed tachyzoites was evaluated by inoculation of the naïve parasite to the survived mice.

Results:

The LD₅₀ of 2-(naphthalene-2-ylthio)-1H-indole was 57 μmol. The longevity of mice was dose dependent. Five mice out of group 400μmol and 3 out of group 800μmol showed immunization to the parasite.

Conclusion:

Our findings demonstrated the toxoplasmocidal activity of the compound. The presence of a well-organized transporter mechanism for indole compounds within the parasite in conjunction with several effective mechanisms of these compounds on Toxoplasma viability would open a window for production of new drugs and vaccines.     

Hantzsch reaction: synthesis and characterization of some new 1,4-dihydropyridine derivatives as potent antimicrobial and antioxidant agents

In the present study two new series of Hantzsch 1,4-dihydropyridine derivatives (1,4-DHPs) containing substituted pyrazole moiety (4a–f and 5a–f) were synthesized by the reaction of 3-aryl-1H-pyrazole-4-carbaldehydes with 1,3-dicarbonylcompounds (ethylacetoacetate and methylacetoacetate) and ammonium acetate. The newly synthesized compounds were characterized by IR, NMR, mass spectral study and also by C, H, N analyses. New compounds were screened for their antimicrobial activity by well plate method (zone of inhibition). Antioxidant studies of the synthesized compounds were also performed by measuring the DPPH radical scavenging assay. Compounds 4c, 4e and 4f were found to be potent antibacterial and antioxidant agents. The acute oral toxicity study for the compounds 4c, 4e and 4f were carried out and the experimental studies revealed that compounds 4c and 4e is safe up to 3000 mg/kg and no death of animals were recorded. However in compound 4f, we found mortality above 2000 mg and also significant behavioral changes in experimental animals.     

New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: design, synthesis, crystal structures, and biological evaluation

Mur ligases (MurC–MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC₅₀ values up to 28 μM. Inhibitor 37, with an IC₅₀ of 34 μM, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128 μg/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization.     

Feruloylacetone as the model compound of half-curcumin: synthesis and antioxidant properties

In order to clarify the contribution of phenolic and enolic hydroxyl group to the antioxidant capacity of feruloylacetone, a model compound of half-curcumin, 6-(p-hydroxy-m-methoxyphenyl)-5-hexene-2,4-dione (FT), 6-(p-benzyloxy-m-methoxyphenyl)-5-hexene-2,4-dione (BMFT), 6-(m,p-dihydroxyphenyl)-5-hexene-2,4-dione (DDFT), 6-(p-hydroxy-m-methoxyphenyl)hexane-2,4-dione (DHFT), 6-(p-hydroxy-m-methoxyphenyl)-5-hexene-2,4-diol (THFT), and ethyl 2-(p-hydroxy-m-methoxybenzylidene)-3-oxobutanoate (EOFT) were synthesized. The radical-scavenging abilities of these compounds were tested by trapping 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS⁺), 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and galvinoxyl radicals. The reductive capacities were screened by quenching singlet oxygen and by inhibiting the oxidation of linoleic acid. They were also employed to inhibit the oxidation of DNA mediated by hydroxyl radical and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). In addition, they were applied to protect erythrocytes against AAPH- and hemin-induced hemolysis. The obtained results revealed that the antioxidant capacity of half-curcumin was derived from the phenolic-OH and the conjugated linkage between phenolic and enolic-OH. The enolic-OH itself cannot trap radicals.     

Isolation and structure elucidation of some components in technical grade chlordane

Seven unknown components in technical chlordane were separated by liquid column chromatography and identified by mass spectrometry and¹H,¹³C-nuclear magnetic resonance. The structure of these components were as follows: 1-@#@ exo,2- endo,4,6,7,8,8 - heptachloro - 3a,4,7,7a — tetrahydro4,7-methanoindane (1), 1 — exo,2 — endo,3 — exo,4,7,8,8-heptachloro- 3a,4,7,7a- tetrahydro - 4,7 — methanoindane (2), 1-exo,2-exo,4,6,7,8,8-heptachloro-3a,4, 7,7a-tetrahydro-4,7-methanoindane (3), 1-@#@ exo,2, 2,4,5(or 6),7,8,8-octachloro — 3a,4,7,7a-tetrahydro4,7-methanoindane (4), 1-exo,2-endo,3-exo,4,5,7, 8,8-octachloro-3a,4,7,7a - tetrahydro-4,7-methanoindane (5), 1-exo,2,2,4,5,6,7,8,8-nonachloro-3a, 4,7,7a — tetrahydro — 4,7-methanoindane (6), tentative, 1 exo,2- exo,3- endo,4,5(or 6),7,8,8-octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindane (7). Compounds1,2, and5 were synthesized by photochemical dechlorination oftrans- chlordane,cis-chlordane, andtrans- nonachlor, respectively. Compound 6 was obtained by addition of chlorine to 2-chloro chlordene. In addition, 1-@#@ exo,2-@#@ exo,3-@#@ exo,4,5,7,8,8-octachloro- 3a,4,7,7a-tetrahydro — 4,7-methanoindane (8), a photodechlorination product ofcis-nonachlor, was found in technical chlordane by gas chromatography/mass spectrometry.     

Construction of the Mobility to Participation Assessment Scale for Stroke (MPASS) and Testing Its Validity and Reliability in Persons With Stroke in Thailand

ObjectivesThis study was conducted to develop the Mobility to Participation Assessment Scale for Stroke (MPASS) and assess its content validity, internal consistency, inter-rater and intra-rater reliability, and convergent validity in people with stroke living in the community.MethodsThe MPASS was developed using published data on mobility-related activity and participation timing in elderly individuals, and then reviewed by community physical therapists. Content validity was established by reaching a consensus of experienced physical therapists in a focus group. The MPASS was scored for 32 participants with stroke (mean age 61.75±4.92 years) by 3 individual testers. Reliability was examined using the intraclass correlation coefficient (ICC), internal consistency using the Cronbach alpha coefficient (α), and convergent validity using the Pearson correlation coefficient (r) to compare the MPASS to the Modified Rivermead Mobility Index as a referent test of mobility.ResultsThe MPASS consists of 8 items, and its scoring system provides information on the ability of people with stroke to reach a movement level enabling them to live in society, including interactions with other people and safe living in the community. The inter-rater and intra-rater reliability were excellent (ICC, 0.948; 95% confidence interval [CI], 0.893 to 0.982 and ICC, 0.967; 95% CI, 0.933 to 0.989, respectively). Internal consistency was good (α=0.877). The convergent validity was moderate (r=0.646; p<0.001).ConclusionsThe newly developed MPASS showed acceptable construct validity and high reliability. The MPASS is suitable for use in people with stroke, especially those who have been discharged and live in the community with the ability to initiate sitting.     

Naringin reduces fat deposition by promoting the expression of lipolysis and β-oxidation related genes

AimsNaringin, a flavonoid present in citrus fruits, has been known for the capacity to reduce lipid synthesis and anti-inflammatory. In this study, we investigated whether naringin increases lipolysis and fatty acid β-oxidation to change fat deposition.MethodsIn in vivo experiment, obese adult mice (20-weeks-old, n = 18) were divided into control group fed with normal diet and naringin-treated group fed with naringin-supplemented diet (5 g/kg) for 60 days, respectively. In in vitro experiment, differentiated 3T3-L1 adipocytes were treated for four days with or without naringin (100 µg/mL).ResultsSupplementing naringin significantly reduced the body weight, abdominal fat weight, blood total cholesterol content of mice, but did not affect food intake. In addition, naringin decreased levels of pro-inflammatory factors in adipose tissue including interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemotactic protein 1 (MCP-1). Naringin increased the expression of AMP-activated protein kinase (AMPK), a key factor in cellular energy metabolism, and raised the ratio of p-AMPK/AMPK in mouse liver tissue. The protein expression of hormone-sensitive lipase (HSL), phospho-HSL563 (p-HSL563), p-HSL563/HSL, and adipocyte triglyceride lipase (ATGL) was significantly increased in the adipose tissue of naringin-treated mice. Furthermore, naringin enhanced the expression of fatty acid β-oxidation genes, including carnitine palmitoyl transferase 1 (CPT1), uncoupling protein 2 (UCP2), and acyl-coenzyme A oxidase 1 (AOX1) in mouse adipose tissue. In in vitro experiment, similar findings were observed in differentiated 3T3-L1 adipocytes with naringin treatment. The treatment remarkably reduced intracellular lipid content, increased the number of mitochondria and promoted the gene expression of HSL, ATGL, CPT1, AOX1, and UCP2 and the phosphorylation of HSL protein.ConclusionNaringin reduced body fat in obese mice and lipid content in differentiated 3T3-L1 adipocytes, which was associated with enhanced AMPK activation and upregulation of the expression of the lipolytic genes HSL, ATGL, and β-oxidation genes CPT1, AOX1, and UCP2.     

Synthesis and anabolic/androgenic evaluation of novel 9α-fluorosteroids

3β,11β-Dihydroxy-9α-fluor-5α-androstane-17-one (2), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane-17-one (3), 3β-acetoxy-9α-fluor-11β,17β-dihydroxy-5α-androstane (4), 3β,17β-diacetoxy-9α-fluor-11β-hydroxy-5α-androstane (5), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane 17β-propionate (6), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane 17β-enanthate (7), 3β-acetoxy-9α-fluor-11β-hydroxy-5α-androstane 17β-isobutyrate (8) were synthesized in the present study. Compounds 2 and 8 exhibited higher anabolic activity than the rest of the synthesized compounds. The structure of all these newly synthesized compounds was confirmed by analytic spectral data (mass, ¹H NMR and ¹³C NMR).     

Pancreatic lipase inhibitory stilbenoids from the roots of Vitis vinifera

Bioassay-guided isolation of an aqueous methanolic extract of Vitis vinifera using pancreatic lipase inhibitory activity led to isolation of seven stilbenoids, wilsonol C (1), heyneanol A (2), ampelopsin A (3), pallidol A (4), cis-piceid (5), trans-piceid (6) and trans-resveratrol (7). The structures were established on the basis of NMR and MS spectroscopic data interpretation. All isolates were evaluated for their inhibitory effects on pancreatic lipase, and stilbenoid 1 exhibited potent inhibitory effect on pancreatic lipase with IC₅₀ values of 6.7?±?0.7?µM.     

Heterocyclic quinones VIII. Synthesis and anti-neoplastic evaluation of 7-substituted-1H-pyrrolo[3,2-c]quinoline-6,9-diones and 3-substituted-11H-indolo[3,2-c]quinoline-1,4-diones

7-Methoxy-2,3,4-trimethyl-1H-pyrrolo[3,2-c]quinoline-6,9-dione 13 and 3-methoxy-6-methyl-11H-indolo-[3,2-c]quinoline-1,4-diones 15 and 19 were obtained by oxidation of quinolinamines 9, 11 and 12 with Fremy's salt. The synthesis method of amines 9 and 11 consists of creating the pyrrole or indole nucleus according to Fisher's indolic reaction applied to hydrazones 8 and 10. Aromatization of 11 yielded quinolinamine 12. The nucleophilic substitution of methoxy by aziridine leads to quinones 14, 16 and 20. These quinones are highly cytotoxic for L1210 cells, but no activity could be established for the P388 lymphocytic leukemia in vivo.     

Synthesis, X-ray structure and cytotoxic effect of nickel(II) complexes with pyrazole ligands

Here we present the synthesis of the new Ni(II) complexes with chelating ligands 1-benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (a), 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (b) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (c). These ligands a–c create solid complexes with Ni(II). The crystal and molecular structures of two complexes were determined by X-ray diffraction method. Thermal stability of two complexes with ligand c by TG/DTG and DSC methods were also shown. Cytotoxic activity of all the complexes against three tumour cell lines and to normal endothelial cells (HUVEC) was also estimated. Complexes with ligand c exhibited relatively high cytotoxic activity towards HL-60 and NALM-6 leukaemia cells and WM-115 melanoma cells. Cytotoxic effectiveness of one of these complexes against melanoma WM-115 cells was two times higher than that of cisplatin. The protonation constant log K = 9.63 of ligand b corresponding to the phenol 2-hydroxy group has been determined in 10% (v/v) DMSO/water solution (25 °C). The coordination modes (formation of two monomeric species: NiL and NiL₂) in the complexes with Ni(II) are discussed for b on the basis of the potentiometric and UV/Vis data.     

Synthesis, hypoxia-selective cytotoxicity of new 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives

We reported the synthesis, hypoxic cytotoxic activities and selectivities of 18 new 3-(alkoxymethylamino)-1,2,4-benzotriazine 1,4-dioxides. The synthesized compounds were screened in vitro against 5 cell lines: K562, SMMC-7721, A549, PC-3 and KB in hypoxia and in normoxia. Some of them showed higher or similar cytotoxic activity when compared to tirapazamine. Physico-chemical study showed the positive correlation between hypoxic activity and lipophilicity within a certain range. Preliminary mechanism study on the potent derivatives 4b, 4l and 4m indicated that the cytotoxic activities of these compounds might be mediated by inducing apoptosis.     

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

ObjectiveA growing body of evidence supports an antiobesity effect of dairy products; however, the mechanisms remain unclear. The objective of this study was to explore possible intestinal mechanisms by which dairy delivers an antiobesity effect. The human intestinal cell line, NCI-H716, was used to test the hypothesis that branched-chain amino acids and dairy proteins regulate satiety hormone secretion and modulate genes involved in fatty acid and cholesterol metabolism.MethodsIn dose–response (0.5%, 1.0%, 2.0%, and 3.0%) studies, the effect of leucine, isoleucine, valine, skim milk, casein, and whey on glucagon-like peptide-1 release and the expression of selected genes were tested.ResultsLeucine, isoleucine, skim milk, and casein stimulated glucagon-like peptide-1 release (P < 0.05). Isoleucine and whey downregulated the expression of intestinal-type fatty acid binding protein (i-FABP), fatty acid transport protein 4 (FATP4), Niemann-Pick C-1–like-1 protein (NPC1L1), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein-2 (SREBP-2), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR; P < 0.05). Leucine and valine downregulated the expression of NPC1L1, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Casein downregulated the expression of i-FABP, FATP4, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Skim milk downregulated the expression of ACC, FAS, and SREBP-2, but not i-FABP, FATP4, and NPC1L1.ConclusionThis work suggests that the antiobesity effect of dairy may be mediated, at least in part, by integration of events that promote glucagon-like peptide-1 secretion and inhibit expression of genes involved in intestinal fatty acid and cholesterol absorption and synthesis.