Dietary Fat and Colon Cancer
Herman Autrup, Gary M. Williams in Experimental Colon Carcinogenesis, 2019
The evidence of the importance of bile acids as colon tumor promoters came from our studies (Table 3).71–74 The development of adenomas increased significantly among those conventional rats initiated with limited amounts of intrarectal MNNG to give a definite low yield of colon cancer and administered with intrarectal lithocholic acid or taurodeoxycholic acid as promoters, compared with the group that was given only the carcinogen. Lithocholic acid applied topically to the colon increased MNNG-induced colon adenocarcinomas in rats. The bile acids themselves did not produce any tumors. A recent study also indicates that the primary bile acids, cholic acid and chenodeoxycholic acid, given intrarectally to conventional rats, also increased MNNG-induced colon tumors and these primary bile acids are subjected to bacterial 7α-dehydroxylation to deoxycholic acid and lithocholic acid, respectively.73 Cohen et al.75 reported that cholic acid in the diet increased MNNG-induced colon carcinogenesis in rats. Total fecal bile acids, particularly deoxycholic acid output, were elevated in animals fed cholic acid as compared with controls. This increase in fecal deoxycholic acid was due to bacterial 7α-dehydroxylation of cholic acid in the colonic contents. These studies demonstrate that these secondary bile acids have a promoting effect in colon carcinogenesis.
Skin
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Targeted subcutaneous fat reduction is an increasingly popular therapeutic target. Deoxycholic acid, (marketed as Kybella) is approved for reduction of submental fat (double chin), and other compounds are under investigation. Investigation of these compounds requires selection of animal models with measurable, consistent subcutaneous fat. Rodents have fat pads that can be collected by a skilled prosector and weighed. Pigs have a good layer of subcutaneous fat and fixed (nonmobile) skin similar to humans. For this reason, they make an ideal model to study subcutaneous fat reduction. The amount of subcutaneous fat can be measured by ultrasound at predetermined timepoints throughout the study. In one author’s experience, occasional young Göttingen strain pigs can have very little subcutaneous fat, so should be screened prior to study start.
Inhibiting the Absorption of Dietary Carbohydrates and Fats with Natural Products
Christophe Wiart in Medicinal Plants in Asia for Metabolic Syndrome, 2017
Anthocyanin-rich extract of Brassica oleracea L. (Figure 1.12) given orally to Charles Foster rats for 8 weeks at a dose of 100 mg/kg/day reduced plasma cholesterol from 216.7 to 92.1 mg/dL and triglycerides from 90.5 to 69.6 mg/dL, low density lipoproteins from 230.8 to 67.3 mg/dL, and very low-density lipoproteins from 18.1 to 13.2 mg/dL.58 This treatment increased triglyceride faeces from 5 to 12.3 mg/g, increased faeces cholesterol from 5.4 to 9 mg/g, and boosted the fecal excression of cholic acid and deoxycholic acid implying the inhibition of cholesterol and triglycerides intestinal absorption.58
pH-sensitive chitosan-deoxycholic acid/alginate nanoparticles for oral insulin delivery
Published in Pharmaceutical Development and Technology, 2021
Ya-Wen Zhang, Ling-Lan Tu, Zhan Tang, Qiao Wang, Gao-Li Zheng, Li-Na Yin
Chitosan (CS) is a biodegradable, biocompatible (Kean and Thanou 2010; Nagpal et al. 2010), and non-immunogenic natural polycationic polymer with mucoadhesive properties (Takeuchi et al. 2005; Thongborisute et al. 2006; Amidi et al. 2010). Chitosan has been shown to prolong drug-resident time in the GI tract (Luessen et al. 1996) and enhance intestinal absorption by opening tight junctions between epithelial cells (Artursson et al. 1994; Schipper et al. 1997). Besides, CS nanoparticles can be prepared in a mild aqueous medium, thereby ensuring their stability during the encapsulation of environmentally sensitive peptides/proteins (Amidi et al. 2010; Kean and Thanou 2010). However, insulin-entrapped chitosan nanoparticles are pH-responsive, therefore they rapidly dissociate in the acidic gastric environment. This characteristic limits the biomedical applications of CS, so it is necessary to modify chitosan to improve the stability of nanoparticles. Deoxycholic acid is a secondary bile acid that can improve oral bioavailability by promoting intestinal epithelial absorption (Samstein et al. 2008; Chaturvedi et al. 2015), which has been shown to be the primary limitation for oral insulin (Park et al. 2004; Lee et al. 2005; Lakkireddy et al. 2016). In this study, CS modified with deoxycholic acid (DCA) was synthesized and used as a nanocarrier to load the model protein drug insulin.
Recent advances from metabolomics and lipidomics application in alzheimer’s disease inspiring drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Miroslava Cuperlovic-Culf, Amanpreet Badhwar
Bile acids (BA) are produced in cholesterol metabolism in human cells [55] and in the gut microbiome and are involved in the digestion of lipids and absorption of fat-soluble vitamins. Correlation in the concentrations of different BA has been analyzed in relation to accumulations of β-amyloid, tau with regards to neurodegeneration. A recent study by Nho et al. [56] explored the association between several serum-based BA and amyloid, tau and neurogeneration markers in AD. Dehkordi et al. [57] have shown significantly lower serum concentrations of primary BA such as cholic acid exist in AD patients. At the same time, serum levels of bacterially produced, secondary BA, such as deoxycholic acid were increased in AD sufferers (Figure 2 shows selected steps in BA biosynthesis with major concentration changes in AD indicated with a white arrow). In fact, in both serum and brain samples, an increase in the deoxycholic acid/cholic acid ratio was strongly associated with cognitive decline. Interestingly, deoxycholic acid emulsifies and solubilizes dietary fats in the intestine. When injected subcutaneously, it disrupts cell membranes in adipocytes and destroys fat cells in that tissue. In 2015, deoxycholic acid was approved by the FDA for the treatment of submental fat to improve esthetic appearance and reduce facial fullness or convexity due to its function in destroying fat cells when injected into the body (FDA Reference ID: 4,208,989).
Changes in intestinal bacteria and imbalances of metabolites induced in the intestines of pancreatic ductal adenocarcinoma patients in a Japanese population: a preliminary result
Published in Scandinavian Journal of Gastroenterology, 2023
Senju Hashimoto, Takumi Tochio, Kohei Funasaka, Kazuki Funahashi, Tenagy Hartanto, Yuka Togashi, Misa Saito, Yuichiro Nishimoto, Mizuguchi Yoshinori, Kazunori Nakaoka, Ayako Watanabe, Mitsuo Nagasaka, Yoshihito Nakagawa, Ryoji Miyahara, Tomoyuki Shibata, Yoshiki Hirooka
In summary, our preliminary study in the Japanese cohort showed that the intestinal environment in PDAC-bt underwent changes characterized by the imbalance in specific intestinal bacteria and metabolites. To the best of our knowledge, our data demonstrated that intestinal microbiota profiles shared similar features in pancreatic cancers and across races, thus suggesting a strong association of intestinal microbiota with the PDAC-bt. We also showed metabolic alterations such as deoxycholic acid and propionic acid in PDAC-bt, which indicate that disruption of the intestinal environment in PDAC-bt may be related to decreased nutrient absorption in the intestine. The observations may have implications for elucidation of novel mechanisms in PDAC-bt and therapeutic strategies using probiotics/prebiotics that improves the intestinal environment.
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