Surprising absence of heparin in the intestinal mucosa of baby pigs.
*antibiotics; *heparin; *intestine; *microbiome; *pig; Animals; Anticoagulants/*metabolism; Chondroitin Sulfates/metabolism; Heparin/biosynthesis/isolation & purification/*metabolism; Heparitin Sulfate/metabolism; Intestinal Mucosa/*metabolism; Mast Cells/metabolism; Newborn/*metabolism; Swine
Heparin, a member of a family of molecules called glycosaminoglycans, is biosynthesized in mucosal mast cells. This important anticoagulant polysaccharide is primarily produced by extraction of the mast cell-rich intestinal mucosa of hogs. There is concern about our continued ability to supply sufficient heparin to support the worldwide growth of advanced medical procedures from the static population of adult hogs used as food animals. While the intestinal mucosa of adult pigs is rich in anticoagulant heparin (containing a few hundred milligrams per animal), little is known about how the content of heparin changes with animal age. Using sophisticated mass spectral analysis we discovered that heparin was largely absent from the intestinal mucosa of piglets. Moreover, while the related, nonanticoagulant heparan sulfate glycosaminoglycan was present in significant amounts we found little chondroitin sulfate E also associated with mast cells. Histological evaluation of piglet intestinal mucosa showed a very low mast cell content. Respiratory mast cells have been reported in baby pigs suggesting that there was something unique about the piglets used in the current study. These piglets were raised in the relatively clean environment of a university animal facility and treated with antibiotics over their lifetime resulting in a depleted microbiome that greatly reduced the number of mast cells and heparin content of the intestinal mucosal in these animals. Thus, from the current study it remains unclear whether the lack of intestinal mast cell-derived heparin results from the young age of these animals or their exposure to their depleted microbiome.
Yu Yanlei; Chen Yin; Mikael Paiyz; Zhang Fuming; Stalcup Apryll M; German Rebecca; Gould Francois; Ohlemacher Jocelyn; Zhang Hong; Linhardt Robert J
Glycobiology
2017
2017-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/glycob/cww104" target="_blank" rel="noreferrer noopener">10.1093/glycob/cww104</a>
Intestinal Farnesoid X Receptor and Takeda G Protein Couple Receptor 5 Signaling in Metabolic Regulation.
*Signal Transduction; Animals; Bile Acids and Salts/biosynthesis/metabolism; Cytoplasmic and Nuclear/*metabolism; G-Protein-Coupled/*metabolism; Humans; Intestinal Mucosa/*metabolism; Liver/metabolism; Receptors
Bile acids play a critical role in the regulation of glucose, lipid and energy metabolisms by activating the nuclear bile acid receptor farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (aka takeda G protein couple receptor 5, TGR5) signaling. Paradoxical roles of FXR in the regulation of glucose and lipid metabolism and metabolic disorder have been reported recently. The activation or inhibition of intestinal FXR signaling has been shown to improve insulin and glucose sensitivity and energy metabolism to prevent diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). TGR5 has an anti-inflammatory function in the intestine and stimulates glucagon-like peptide-1 (GLP-1) secretion in the intestine to stimulate insulin secretion from the pancreas. The role of TGR5 in metabolism and metabolic regulation is not clear and warrants further study. FXR and TGR5 are co-expressed in the ileum and colon. These 2 bile acid-activated receptors may cooperate to stimulate GLP-1 secretion and improve hepatic metabolism. FXR and TGR5 dual agonists may have therapeutic potential for treating diabetes and NAFLD.
Chiang John Y L; Pathak Preeti; Liu Hailiang; Donepudi Ajay; Ferrell Jessica; Boehme Shannon
Digestive diseases (Basel, Switzerland)
2017
2017
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1159/000450981" target="_blank" rel="noreferrer noopener">10.1159/000450981</a>