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Genetic Regulation of Intestinal Lipid Transport and Metabolism

49.1 Major Pathways and Genes Involved in Intestinal Lipid Droplet Formation and Triglyceride-Rich Lipoprotein Assembly In summary overview, long-chain fatty acids (LCFAs), whether monomeric or in the form of monoglycerides, represent the major substrate for the generation of triglyceride- rich lipid droplets (LDs) and in turn for the assembly of triglyceride-rich lipoproteins. Apical uptake of LCFAs occurs predominantly in the proximal small intestine (duodenum, jejunum), although…

Enterocyte Fatty Acid Handling Proteins and Chylomicron Formation

Abbreviations ACSL acyl-CoA synthetase long chain ApoAI apolipoprotein AI ApoAIV apolipoprotein AIV ApoB48 apolipoprotein B48 Apobec-1 apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like COP coatomer proteins DAG diacylglycerol DGAT DAG acyltransferase ER endoplasmic reticulum FA fatty acid FABP FA-binding protein FATP fatty acid transport protein G3P sn-3-glycerol phosphate GLP-2 glucagon-like peptide-2 GPAT G3P acyltransferase HDL high-density lipoprotein Hsp heat-shock protein LDL low-density lipoprotein LPAAT acyl-glycerol-3-phosphate O…

Protein Digestion and Absorption

47.1 An Overview of Protein Digestion and Absorption Amino acids constitute an important class of nutrients obligatory for normal function and survival of mammalian cells. These amino acids are classified as essential and nonessential purely based on whether or not the cells have the ability to synthesize them. If the cells have the capacity to generate certain amino acids endogenously using other nutrients or metabolites as…

Sugar Absorption

Acknowledgments We are indebted to our colleagues and collaborators who have made major contributions to our research on SGLTs, and grants from the National Institutes of Health that provided financial support. As in animals, humans need to eat, digest, and absorb food to grow and conduct their daily activities. Glucose contained in the diet and synthesized in the liver and other organs is a central unit…

Molecular Mechanisms of Polarized Protein Trafficking in Epithelial Cells

45.1 Introduction to Epithelial Cell Polarity The ability of epithelial cells in gastrointestinal (GI) track to absorb selected nutrients while secreting electrolytes, enzymes, and digestive factors depends on intracellular trafficking mechanisms that establish and maintain the polarized disruption of different transport proteins and surface receptors on the apical and basolateral membranes. A combination of intracellular sorting operations, vectorial delivery mechanisms, plasmalemma-specific fusion, and retention processes are…

Physiology of Cholngiocytes

Cholangiocytes are epithelial cells that line the biliary tree, a complex, three-dimensional network of interconnecting intrahepatic and extrahepatic bile ducts. The main physiologic function of cholangiocytes is the modification of the bile within the ductal lumen via coordinated bidirectional vectorial transport of ions, solutes, and water. These complex processes are regulated by extracellular signaling molecules (i.e., hormones, neurotransmitters, regulatory peptides, nucleotides), components of bile (i.e., bile…

Mechanisms of Hepatocyte Detoxification

43.1 Introduction 43.1.1 Liver Anatomy and Function The cell types within the liver consist of hepatocytes, biliary epithelial cells, sinusoidal-lining cells (Kupffer cells and endothelial cells), stellate cells (formerly known as Ito cells), and cells involved in the immune response. Hepatocytes are the predominant cells in the liver. These highly specialized cells perform a wide range of metabolic activities. Hepatocytes are responsible for the synthesis of…

Mechanisms of Hepatocyte Organic Anion Transport

42.1 Introduction One of the major functions of the hepatocyte is the removal of organic anionic compounds from the blood. These compounds include various xenobiotics as well as endogenous compounds such as bilirubin and bile acids. Many of these compounds have limited aqueous solubility and circulate bound to serum albumin. Despite being almost entirely protein bound, for the most part these organic anions are cleared rapidly…

Bile Formation and the Enterohepatic Circulation

41.1 Introduction Bile is a complex aqueous secretion that originates from hepatocytes and is modified distally by the biliary epithelium. As a basic “humor” in the body, the significance of bile had been recognized since antiquity. However, our understanding of bile was originally restricted to knowledge of its composition, and the mechanism of bile formation remained elusive until the mid-20th century with the advent of techniques…

Regulation of Pancreatic Secretion

Pancreatic secretion is regulated by highly integrated neural and hormonal influences that involve the brain, enteric nervous system, and gastrointestinal tract. Although these processes are complex they illustrate the finely regulated nature that is needed for maintaining sufficient secretion of pancreatic enzymes that are essential for adequate ingestion and digestion of nutrients. Another source of information about the regulation of exocrine pancreatic physiology can be found…

Structure-Function Relationships in the Pancreatic Acinar Cell

Acknowledgments Support for the investigative activities of FSG come from the NIH (DK 52401 and DK098108) and a Veterans Administration Merit Award and for SP DK098108. The authors also wish to thank Professor Guy Groblewski for reviewing sections of this chapter. 39.1 Organization of the Exocrine Pancreas The pancreas is a retroperitoneal organ that is composed of the exocrine and endocrine glands. About 85% of the…

The Cell Biology of Gastric Acid Secretion

38.1 Cellular Plasticity of Gastric Acid Secretion 38.1.1 Organization of Epithelial Cells in the Stomach The stomach is organized by five concentric tissue layers: (1) the mucosal epithelium, lining the lumen of the stomach; (2) a thin layer of smooth muscle called the muscularis mucosae; (3) the submucosa consisting of connective tissue and blood vessels; (4) the tunica muscularis, composed of two layers (inner circular and…

Salivary Gland Secretion

37.1 Introduction Saliva is produced by salivary glands in a range of animal species and fulfills many different functions. Of particular importance are its roles in nutrition, facilitating the chewing, tasting, digestion, and swallowing of food. Striking dietary related adaptations in salivary gland structure and physiology are seen in mammals, reptiles, and invertebrates. For example, the production of venom in order to immobilize prey has evolved…

Microbial Physiology of the Digestive Tract and Its Role in Inflammatory Bowel Diseases

There is a growing appreciation for the importance of gastrointestinal (GI) microbes in human health and disease. However, which microbes are important and how they contribute to human health and disease are only beginning to be understood. In this chapter, we will discuss how the relationship between host and microbe is established and how a healthy relationship contributes to the health of the GI tract. We…

Gut Microbiome and Metabolism

35.1 Introduction: Microbiota: The Intestine’s Best Frenemy Forever The mammalian intestine is inhabited by a diverse collection of microorganisms collectively referred to as the gut microbiota. While the accuracy of the often-cited estimate that the human gut contains about 100 trillion bacteria has recently been questioned, in any case, there are certainly a lot of bacteria present and there is strong evidence that they impact numerous…

Influence of the Gut Microbiome on Immune Development During Early Life

34.1 Introduction The gastrointestinal tract harbors the largest population of commensal organisms in the human body, whose homeostasis requires immunoregulatory mechanisms to prevent unnecessary activation of the immune system against antigens generated by environmental exposures including host-associated microbes. The establishment of immunological tolerance is a result of proper education of resident and newly immigrated immune populations suggesting a dynamic and active relationship between the nascent and…

Diet Effects on Gut Microbiome Composition, Function, and Host Physiology

Abbreviations DIO diet-induced obesity FFA free fatty acid FOS fructo-oligosaccharides GOS galacto-oligosaccharides HFD high fat diet HMO human milk oligosaccharides LPS lipopolysaccharide PBA primary bile acid RYGB Roux-en-Y gastric bypass SBA secondary bile acid SCFA short-chain fatty acid WD western diet 33.1 Introduction Diet has long been implicated in a suite of specific physiological outcomes in the host, ranging from obesity, to cancer, to risk of…

Gastrointestinal Microbial Ecology With Perspectives on Health and Disease

32.1 Introduction The human gut is one of the most diverse and rich ecosystems on Earth. It has been estimated that each person is home to over 100 trillion (10 14 ) bacterial and archaeal cells. This number is impressive when you consider that the sum total of all human cells in an individual person is approximately 10 trillion (10 13 ). The highest bacterial and…

Intestinal Tuft Cells

31.1 Overview Since their discovery > 60 years ago, tuft cells have intrigued and mystified researchers. Early studies focused on the unique morphology of tuft cells and their distribution pattern across mucosal surfaces, but their function remained unknown. The last 10 years have finally brought rapid advances in our understanding of intestinal tuft cells, including: (1) a detailed characterization of tuft cell ontogeny and associated lineage-specific…

Luminal Chemosensing and Mucosal Defenses in the Upper GI Tract

30.1 Duodenal Chemosensing Patterns and Mucosal Defense Factors The identification of luminal chemosensors in the gastrointestinal (GI) tract has emerged in part from the de-orphanization and characterization of nutrient-sensing G protein-coupled receptors (GPCRs) in the most recent decade. Since luminal chemical substances including nutrients or meal components, or endogenously secreted molecules such as gastric acid, digestive enzymes, and bile acids release gut hormones or neurotransmitters, gut…