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. 2015 Nov 1;151:198-206.
doi: 10.1016/j.physbeh.2015.07.009. Epub 2015 Jul 11.

Lipid Transport in Cholecystokinin Knockout Mice

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Free PMC article

Lipid Transport in Cholecystokinin Knockout Mice

Alexandra King et al. Physiol Behav. .
Free PMC article

Abstract

Cholecystokinin (CCK) is released in response to lipid feeding and regulates pancreatic digestive enzymes vital to the absorption of nutrients. Our previous reports demonstrated that cholecystokinin knockout (CCK-KO) mice fed for 10 weeks of HFD had reduced body fat mass, but comparable glucose uptake by white adipose tissues and skeletal muscles. We hypothesized that CCK is involved in energy homeostasis and lipid transport from the small intestine to tissues in response to acute treatment with dietary lipids. CCK-KO mice with comparable fat absorption had increased energy expenditure and were resistant to HFD-induced obesity. Using intraduodenal infusion of butter fat and intravenous infusion using Liposyn III, we determined the mechanism of lipid transport from the small intestine to deposition in lymph and adipocytes in CCK-KO mice. CCK-KO mice had delayed secretion of Apo B48-chylomicrons, lipid transport to the lymphatic system, and triglyceride (TG)-derived fatty acid uptake by epididymal fat in response to acute treatment of intraduodenal lipids. In contrast, CCK-KO mice had comparable TG clearance and lipid uptake by white adipocytes in response to TGs in chylomicron-like emulsion. Thus, we concluded that CCK is important for lipid transport and energy expenditure to control body weight in response to dietary lipid feeding.

Keywords: Fat absorption; Fatty acid uptake; Lymph; White adipose tissues.

Figures

Figure 1
Figure 1
Body weight, tissue weight and caloric intake of CCK-KO and WT mice. Body weight (A), Total fat mass (B), fat weight for various fat pads (C), liver weight (D), caloric intake (E), and energy expenditure (F) of CCK-KO and WT mice (n = 8 per group). Animals were fed a low-fat chow diet (LFD) or HFD for 10 wk. Data are expressed as mean ± SEM and values with an asterisk represent significant differences between groups (P < 0.05).
Figure 2
Figure 2
Fat absorption of CCK-KO and WT mice. Total fat absorption (A) and fatty acid profiles (B) in fecal pellets were determined using a GC system. Fecal pellets were collected on the 4th day after animals (n=7–9 per group) had been consuming a 20% butter fat diet mixture with 5% Olestra during the 9th week on LFD or HFD. Data are expressed as mean ± SEM and values with an asterisk represent significant differences between groups (P < 0.05).
Figure 3
Figure 3
Lymphatic TG transport into lymph. Hourly lymphatic flow rate (A) and lymphatic TG output (B) during continuous intraduodenal infusion of 4 pmoles/h butter fat. Total output of lymphatic TG for 2-h infusion (C) and 6-h infusion. CCK-KO and WT mice (n= 4–5 mice per group) received intraduodenal infusion of a lipid emulsion for 6 h. Data are expressed as mean ± SEM and values with an asterisk represent significant differences between groups (P < 0.05).
Figure 4
Figure 4
Lymphatic apolipoprotein (Apo) B48 secretion in CCK-KO and WT mice. Lymph was collected hourly during the 6 h of continuous intraduodenal infusion of a lipid emulsion for 6 h (n= 4 mice per group); 1-min volumes (based on flow rate) of lymph were analyzed by a 4–20% SDS gel electrophoresis followed by Western blot detection of Apo B48 using a polyclonal antibody in (A). The percentage of hourly Apo B48 secretion divided by base level of Apo B48 (0 h) during the first 3 h of lipid infusion for the CCK-KO and the WT animals (B). Data are expressed as mean ± SEM and values with an asterisk represent significant differences between groups (P < 0.05).
Figure 5
Figure 5
Lipid uptake by adipocytes and lipid clearance in CCK-KO and WT mice. Plasma TG and Cholesterol (A) and 3H-TG-derived fatty acid (B) content in the adipocytes of CCK-KO and WT mice (n = 5 per group) were determined at the end of a 2-h continuously intraduodenal infusion of 4 pmoles/h butter fat and 3H-TG. Plasma clearance of triglyceride (C) in CCK-KO and WT mice were determined at 2–30 min postinjection, and radioactive levels of TG-derived fatty acids (D) in the adipocytes of CCK-KO and WT mice was determined at 30-min postinjection. CCK-KO and WT mice (n= 6–7 per group) intravenously received an intravenous infusion of radioactive fat emulsion (Lyposyn III) and blood was collected 0 to 30 min. Radioactive lipids in plasma and adipocytes were determined by scintillation counting. Data are expressed as mean ± SEM and values with an asterisk represent significant differences between groups (P < 0.05).

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