Disruption of the murine intestinal alkaline phosphatase gene Akp3 impairs lipid transcytosis and induces visceral fat accumulation and hepatic steatosis

2007 ◽  
Vol 292 (5) ◽  
pp. G1439-G1449 ◽  
Author(s):  
Takanari Nakano ◽  
Ikuo Inoue ◽  
Iwao Koyama ◽  
Kenta Kanazawa ◽  
Koh-ichi Nakamura ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight ◽  
Weight Gain ◽  
Visceral Fat ◽  
Corn Oil ◽  
Body Weight Gain ◽  
Lipid Absorption ◽  
Wild Type ◽  
Intestinal Alkaline Phosphatase ◽  
Visceral Fat Accumulation

Intestinal alkaline phosphatase (IAP) is involved in the process of fat absorption, a conclusion confirmed by an altered lipid transport and a faster body weight gain from 10 to 30 wk in both male and female mice with a homozygous null mutation of the IAP coding gene ( Akp3−/− mice). This study was aimed to delineate morphologically and quantitatively the accelerated lipid absorption in male Akp3−/− mice. Feeding a corn oil bolus produced an earlier peak of triacylglycerol in serum (2 vs. 4 h for Akp3−/− and wild-type mice, respectively) and an approximately twofold increase in serum triacylglycerol concentration in Akp3−/− mice injected with a lipolysis inhibitor, Triton WR-1339. A corn oil load induced the threefold enlargement of the Golgi vacuoles in male wild-type mice but not in Akp3−/− mice, indicating that absorbed lipids rarely reached the Golgi complex and that the transcytosis of lipid droplets does not follow the normal pathway in male Akp3−/− mice. Force feeding an exaggerated fat intake by a 30% fat chow for 10 wk induced obesity in both male Akp3−/− and wild-type mice, and therefore no phenotypic difference was observed between the two. On the other hand, the forced high-fat chow induced an 18% greater body weight gain, hepatic steatosis, and visceral fat accumulation in female Akp3−/− mice but not in female wild-type controls. These results provide further evidence that IAP is involved in the regulation of the lipid absorption process and that its absence leads to progressive metabolic abnormalities in certain fat-forced conditions.

Bimatoprost promotes satiety and attenuates body weight in rats fed standard or obesity-promoting diets.

2020 ◽  
Author(s):  
Clayton Spada ◽  
Chau Vu ◽  
Iona Raymond ◽  
Warren Tong ◽  
Chia-Lin Chuang ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Gastric Emptying ◽  
Food Intake ◽  
Visceral Fat ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Sprague Dawley ◽  
Hormone Levels ◽  
Gut Hormone

Abstract Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.

scholarly journals Over-expression of miR-34c leads to early-life visceral fat accumulation and insulin resistance

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Philip H. Jones ◽  
Brian Deng ◽  
Jessica Winkler ◽  
Arin L. Zirnheld ◽  
Sarah Ehringer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Animal Model ◽  
Weight Gain ◽  
Fat Mass ◽  
Visceral Fat ◽  
Early Life ◽  
Body Weight Gain ◽  
Late Life ◽  
Preventive Strategy ◽  
Visceral Fat Accumulation

Abstract Overweight children and adolescents are at high risk for adult and late life obesity. This report investigates some underlying mechanisms contributing to obesity during early life in an animal model. We generated a strain of transgenic mice, cU2, overexpressing human microRNA 34c, a microRNA functionally implicated in adipogenesis. Male and female cU2 mice exhibit significant weight gain, accompanied by marked increase in abdominal fat mass and metabolic abnormalities, including reduction of both glucose clearance rate and insulin sensitivity, as early as two months of age. Adipogenesis derailment at this early age is suggested by decreased expression of adiponectin, the fat mass and obesity-associated gene, and the adiponectin receptor R1, coupled with a reduction of the brown fat biomarker PAT2 and the adipogenesis inhibitor SIRT1. Notably, adiponectin is an important adipokine and an essential regulator of glucose and fatty acid homeostasis. cU2 mice may provide a crucial animal model for investigating the role of miR-34c in early onset insulin resistance and visceral fat mass increase, contributing to accelerated body weight gain and metabolic disorders. Intervention in this dysregulation may open a new preventive strategy to control early-life weight gain and abnormal insulin resistance, and thus prevalent adult and late life obesity.

scholarly journals Effect of Sage Extract on Alkaline Phosphatase, Enterocyte Proliferative Activity and Growth Performance in Chickens

2010 ◽  
Vol 79 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Mikuláš Levkut ◽  
Andrej Marcin ◽  
Ľudovít Lenhardt ◽  
Pavol Porvaz ◽  
Viera Revajová ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight ◽  
Growth Performance ◽  
Proliferative Activity ◽  
Serum Proteins ◽  
Body Weight Gain ◽  
Total Serum ◽  
Intestinal Alkaline Phosphatase ◽  
Total Proteins ◽  
Proliferative Ability

The effects of sage extract on the activity of intestinal alkaline phosphatase (AP), proliferative ability of enterocytes, and growth performance in chickens were studied during 42 days of the experiment under commercial conditions. A significant increase of body weight gain was found in chickens fed with sage extract in the grower period (17-29 days of age) and in the finisher period (30-42 day of age). Total serum proteins were significantly (p< 0.05) increased at 29 days of age in animals treated with sage extract. A significant (p< 0.001) decrease in activity of intestinal AP was demonstrated on 29 and 42 days in animals fed with sage extract complemented diet. Proliferative activity of enterocytes was increased (p< 0.01) in the finisher period along the duodenal villi in animals treated with sage extract. We conclude that the higher growth performance was probably due to improved endogenous secretion of the liver as a consequence of increased total proteins mainly in the grower period. Decreased activity of intestinal alkaline phosphatase was not in correlation with proliferative ability of enterocytes and the lower activity of AP could be influenced by improved digestion of lipids.

scholarly journals Early type 2 diabetes and obesity does not affect eicosanoids level and renal morphology in a rat model/ Diabetes tipo 2 no estágio inicial e obesidade não afetam o nível de eicosanóides e a morfologia renal em um modelo de rato

2021 ◽  
Vol 7 (8) ◽  
pp. 85230-85249
Author(s):  
Sandra Aparecida Benite Ribeiro ◽  
Kamila Lauany Lucas Lima ◽  
Júlia Matzenbacher dos Santos ◽  
Didier Quevedo Cagnini ◽  
Igo Gomes Guimarães ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Blood Glucose ◽  
Visceral Fat ◽  
Feed Efficiency ◽  
Body Weight Gain ◽  
Caloric Intake ◽  
Renal Tissue ◽  
Standard Diet ◽  
High Fat

This study evaluated the effects of the early development of Diabetes Mellitus 2 (T2D) and diet-induced Obesity in the eicosanoid pathways and its effects on renal tissue. Thirty male Wistar rats were fed with a high-fat or standard diet and were divided into 3 groups: The Control group received a standard diet, the T2D group received a high-fat diet and a single dose of streptozotocin (25mg/Kg) and the Obesity group received high-fat diet. Caloric intake, feed efficiency, body weight gain, visceral fat, blood glucose, plasma levels of 14,15 EET/DHET, 20-HETE, and kidneys’ morphology were analyzed. Total caloric intake and feed efficiency were higher in the animals of the Obesity group than in Control.  Body weight gain, visceral fat, and blood glucose were higher in Obesity and T2D induced groups than in Control. Body weight gain, visceral fat, and feed efficiency associated positively with blood glucose. However, there was no difference in 14,15 EET/DHET, 20-HETE levels, or kidney injury between groups. In conclusion, we were unable to assess whether changes in eicosanoids are due to obesity or diabetes induction. So, this study suggests that longer periods of homeostatic disturbance caused by these protocols seem to be necessary to induce complications related to the disruption of the eicosanoid’s pathway and its effects on renal tissue. 

METABOLIC EFFECTS OF MONOAMINE OXIDASE INHIBITORS ON THE RAT PITUITARY

1967 ◽  
Vol 39 (1) ◽  
pp. 1-6 ◽  
Author(s):  
U. ZOR ◽  
J. SHORE ◽  
D. LOCKER ◽  
F. G. SULMAN
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight ◽  
Weight Gain ◽  
Monoamine Oxidase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Dna And Rna ◽  
Production Body

SUMMARY Five monoamine oxidase inhibitors (MAOI) were tested for a correlation between MAO blocking potency, the effect on somatotrophic hormone (STH) production and metabolic effects on the pituitary. Mebanazine, N-acetyl-mebanazine and pargyline inhibited STH production, body weight gain and glucose-6-phosphate (G-6-P) dehydrogenase activity. MAOI which contain a hydrazine group (mebanazine and N-acetyl-mebanazine) also inhibited alkaline phosphatase activity as well as DNA and RNA formation in the pituitary, while pargyline, which contains an amino group, was inactive in these respects. Iproniazid and norpargyline were inactive with regard to STH production, body-weight gain and metabolic activities of the pituitary: alkaline phosphatase activity, G-6-P dehydrogenase activity, and DNA and RNA content. This suggests a relation between the ability of an MAOI to inhibit STH production and inhibition of the phosphogluconate oxidative pathway.

scholarly journals Accelerated Fat Absorption in Intestinal Alkaline Phosphatase Knockout Mice

2003 ◽  
Vol 23 (21) ◽  
pp. 7525-7530 ◽  
Author(s):  
Sonoko Narisawa ◽  
Lei Huang ◽  
Arata Iwasaki ◽  
Hideaki Hasegawa ◽  
David H. Alpers ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight Gain ◽  
Serum Triglyceride ◽  
Fat Absorption ◽  
Wild Type ◽  
Intestinal Alkaline Phosphatase ◽  
Rate Limiting Step ◽  
Deficient Mice

ABSTRACT Intestinal alkaline phosphatase (IAP) is the most ancestral of the tissue-specific members of the AP gene family. Several studies have suggested an absorptive function for IAP, but in vivo data to this effect have been lacking. We inactivated the mouse IAP gene in embryo-derived stem cells and generated mice homozygous for the null mutation. The mice were macroscopically and histologically normal and fertile and showed no difference from the wild-type controls under normal laboratory conditions. However, when maintained long-term on a high-fat diet, the IAP-deficient mice showed faster body weight gain than did control animals. Histological examination revealed an accelerated transport of fat droplets through the intestinal epithelium and elevation of serum triglyceride levels in the IAP-deficient mice compared to wild-type mice. Our study suggests that IAP participates in a rate-limiting step regulating fat absorption.

Contribution of energy intake and tissue enzymatic profile to body weight gain in high-fat-fed rats

1997 ◽  
Vol 272 (1) ◽  
pp. R188-R194 ◽  
Author(s):  
E. C. Gayles ◽  
M. J. Pagliassotti ◽  
P. A. Prach ◽  
T. A. Koppenhafer ◽  
J. O. Hill
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Energy Intake ◽  
Gastrocnemius Muscle ◽  
Corn Oil ◽  
Body Weight Gain ◽  
High Fat ◽  
Beta Oxidation ◽  
Enzymatic Profile ◽  
Time Point

The purpose of the current study was to examine the enzymatic profile [phosphofructokinase (PFK), beta-hydroxyacyl-CoA dehydrogenase (HADH), and citrate synthase (CS)] in gastrocnemius muscle, heart, and liver in rats allowed ad libitum access to a high-fat diet (HFD, 45% of kcal from corn oil). Male Wistar rats were fed a low-fat diet (LFD, 12% of kcal from corn oil) for a 2-wk baseline period after which some continued on the LFD and others were placed on the HFD. After 1 wk on the HFD, rats were categorized as obesity-resistant (OR), -intermediate (OI), or -prone (OP) on the basis of body weight gain (OR, lower tertile; OI, middle tertile; OP, upper tertile). At 1, 2, and 5 wk, rats from each group were killed (n = 9-14 from each group/time point) after a 24-h fast. At the end of the 5-wk dietary period, weight gain was 114.8 +/- 4.3 in LFD, 125.2 +/- 3.7 in OR, 147.1 +/- 4.1 in OI, and 173.7 +/- 3.5 g in OP rats (OP > OI > OR, LFD; P < 0.001). Energy intake was highly correlated with weight gain on the HFD at each time point (r > or = 0.72, P < 0.001). After 1 wk on the HFD, significant correlations between the ratio of PFK/HADH (an indication of the relative capacity for glycolysis vs. beta-oxidation, r = 0.4, P = 0.03) and HADH/CS (an indication of the capacity for beta-oxidation relative to total oxidative capacity, r = -0.56, P = 0.001) in the gastrocnemius muscle and weight gain were observed. At week 2, significant correlations between these ratios and weight gain were observed in the gastrocnemius, liver, and heart. In contrast, these ratios were not significantly correlated with weight gain at 5 wk. These results suggest that rats most susceptible to weight gain or a HFD are characterized by a continuous increase in energy intake (explaining approximately 50% of the variance in weight gain) and an early tissue enzymatic profile that favors carbohydrate over fat use.

scholarly journals Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired fat absorption

2017 ◽  
Vol 313 (2) ◽  
pp. E121-E133 ◽  
Author(s):  
Enrico Bertaggia ◽  
Kristian K. Jensen ◽  
Jose Castro-Perez ◽  
Yimeng Xu ◽  
Gilbert Di Paolo ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Hepatic Steatosis ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Western Diet ◽  
Lipid Absorption ◽  
Whole Body ◽  
Diabetes Therapy ◽  
Body Energy

Bile acids (BAs) are cholesterol derivatives that regulate lipid metabolism, through their dual abilities to promote lipid absorption and activate BA receptors. However, different BA species have varying abilities to perform these functions. Eliminating 12α-hydroxy BAs in mice via Cyp8b1 knockout causes low body weight and improved glucose tolerance. The goal of this study was to determine mechanisms of low body weight in Cyp8b1−/− mice. We challenged Cyp8b1−/− mice with a Western-type diet and assessed body weight and composition. We measured energy expenditure, fecal calories, and lipid absorption and performed lipidomic studies on feces and intestine. We investigated the requirement for dietary fat in the phenotype using a fat-free diet. Cyp8b1−/− mice were resistant to Western diet-induced body weight gain, hepatic steatosis, and insulin resistance. These changes were associated with increased fecal calories, due to malabsorption of hydrolyzed dietary triglycerides. This was reversed by treating the mice with taurocholic acid, the major 12α-hydroxylated BA species. The improvements in body weight and steatosis were normalized by feeding mice a fat-free diet. The effects of BA composition on intestinal lipid handling are important for whole body energy homeostasis. Thus modulating BA composition is a potential tool for obesity or diabetes therapy.

Chronic high corticosterone with voluntary corn oil ingestion induces significant body weight gain in mice

2019 ◽  
Vol 204 ◽  
pp. 112-120 ◽  
Author(s):  
Shigenobu Matsumura ◽  
Mayuki Odanaka ◽  
Fuka Ishikawa ◽  
Tsutomu Sasaki ◽  
Mark Christian C. Manio ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Corn Oil ◽  
Body Weight Gain
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