Lipid transport in cholecystokinin knockout mice

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 a 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 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 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 introdudenal lipids. In contrast, CCK-KO mice had comparable TG clearance and lipid uptake by white adipocytes in response to TG 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.

The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

“…Moreover, CCK‐8 effects appeared to be insulin‐dependent and, in the case of subcutaneous WAT, linked to the activation of PPARγ. Taken together, our findings support the concept, already suggested by previous studies carried out by our group and others (King, Yang, Huesman, Rider, & Lo, ; Plaza, Merino, Cano, et al, ; Plaza, Merino, Sánchez‐Pernaute, et al, ), that both CCK and CCK binding sites have a relevant role in modulating WAT homeostasis, particularly in the case of Sc‐WAT.…”

Cholecystokinin is involved in triglyceride fatty acid uptake by rat adipose tissue

“…This regulation would be accomplished by: (i) limiting food intake; (ii) delaying gastric emptying; (iii) facilitating intestinal digestion of fat and TG absorption and (iv) enhancing fatty acid (FA) catabolism in oxidative tissues. More recently, King and coworkers demonstrated that FA uptake by adipose tissue in CCK-knockout mice is impaired (King et al 2015, Weng et al 2017. In a recent study, Demenis et al (2017) reported that CCK-8 promotes CD-36-mediated FA uptake by mouse enterocytes.…”

Sulfated Cholecystokinin-8 Promotes CD36—Mediated Fatty Acid Uptake into Primary Mouse Duodenal Enterocytes

“…The proposition that CCK induces an increase in enterocyte FA to facilitate nutrient absorption is supported by reported findings in CCK-KO mice (King et al, 2015 ). In response to acute intraduodenal introduction of lipids mice lacking CCK were observed to have delayed secretion of Apo B48-chylomicrons and lipid transport to the lymphatic system.…”

“…In response to acute intraduodenal introduction of lipids mice lacking CCK were observed to have delayed secretion of Apo B48-chylomicrons and lipid transport to the lymphatic system. Both of these effects are indicative of impaired FA uptake into enterocytes compared to wild type animals and support a physiological role for CCK-induced lipid absorption (King et al, 2015 ).…”

“…Surprisingly, there is a scarcity of published research pertaining to a possible action of CCK to promote nutrient uptake, although indirect evidence is apparent that may point to this action (e.g., King et al, 2015 ). Given that CCK is secreted in response to fats we reasoned that CCK, like GLP-2 or OEA, may induce effects that facilitate FA absorption (McLaughlin et al, 1999 ).…”