Considerable evidence indicates that the ingestion of a high-fat (HF) diet predisposes humans and animals to obesity. The applicants hypothesize that: (1) apolipoprotein A-IV (apo A-IV) is an endogenous signal for fat absorption by gastrointestinal apo A-IV production and secretion in response to lipids in the gastrointestinal tract; (2) chronic high-fat diets alter the metabolism of chylomicron (CM) by altering its physiochemical nature; and (3) chronic consumption of a high-fat diet increases the secretion and/or action of intestinal factors that facilitate fat absorption and predispose the body to increase the storage of fat in adipose tissue.
SPECIFIC AIM 1. The applicants will determine the dose-response relationship between the dose of lipid fed and the mRNA levels, synthesis and secretion of apo A-IV by the jejunum in animals fed chronically HF compared to low-fat (LF). They will also compare the A-IV response to lipid feeding in jejunum and in ileum and also the type of fat. In addition, they will determine if apo A-IV may be involved in the long-term regulation of food intake and body weight regulation. Specifically, they will use the apo A-IV knockout and transgenic mouse to address this question.
SPECIFIC AIM 2. The applicants will test the hypothesis that chronic HF diets alter the metabolism of CM by studying the plasma removal of both the labeled triglyceride and cholesterol ester moieties of the chylomicron (CM) from the HF and LF animals.
SPECIFIC AIM 3. The applicants recently discovered that the small intestine secretes glucose in response to a lipid meal and that the glucose concentration in lymph is directly proportional to the amount of lipid transported by the small intestine (r = +0.97). They will test the hypothesis that the gut secretes glucose during lipid absorption and that the gut and/or the lymphatic ducts detect this intestinally-derived de novo glucose. They further hypothesize that the amount of glucose acts as a signal indicating the amount of fat being transported by the small intestine. A corollary hypothesis is that the amount of glucose synthesized and released per unit of fat absorbed, or else the impact of this glucose signaling, is altered by high-fat feeding. In addition, the apo A-IV knockout and transgenic animals will be used to determine if there is interaction between the lymph glucose and lymph apo A-IV signals.
| Ji, Yong; Sakata, Yasuhisa; Li, Xiaoming et al. (2013) Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release. Am J Physiol Gastrointest Liver Physiol 304:G732-40 |
| Lu, Wendell J; Yang, Qing; Yang, Li et al. (2012) Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP. Lipids 47:571-80 |
| Clegg, Deborah J; Gotoh, Koro; Kemp, Christopher et al. (2011) Consumption of a high-fat diet induces central insulin resistance independent of adiposity. Physiol Behav 103:10-6 |
| Lo, Chun-Min; Xu, Min; Yang, Qing et al. (2009) Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration. Am J Physiol Regul Integr Comp Physiol 296:R43-50 |
| Lo, Chun-Min; Nordskog, Brian K; Nauli, Andromeda M et al. (2008) Why does the gut choose apolipoprotein B48 but not B100 for chylomicron formation? Am J Physiol Gastrointest Liver Physiol 294:G344-52 |
| Shen, Ling; Tso, Patrick; Woods, Stephen C et al. (2008) Brain apolipoprotein E: an important regulator of food intake in rats. Diabetes 57:2092-8 |
| Lu, Wendell J; Yang, Qing; Sun, William et al. (2008) Using the lymph fistula rat model to study the potentiation of GIP secretion by the ingestion of fat and glucose. Am J Physiol Gastrointest Liver Physiol 294:G1130-8 |
| Lo, Chun-Min; Samuelson, Linda C; Chambers, James Brad et al. (2008) Characterization of mice lacking the gene for cholecystokinin. Am J Physiol Regul Integr Comp Physiol 294:R803-10 |
| Lu, Wendell J; Yang, Qing; Sun, William et al. (2007) The regulation of the lymphatic secretion of glucagon-like peptide-1 (GLP-1) by intestinal absorption of fat and carbohydrate. Am J Physiol Gastrointest Liver Physiol 293:G963-71 |
| Lo, Chun Min; Zhang, Dian Ming; Pearson, Kevin et al. (2007) Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake. Am J Physiol Regul Integr Comp Physiol 293:R1490-4 |
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