scholarly journals Blocking β1/β2-Adrenergic Signaling Reduces Dietary Fat Absorption by Suppressing Expression of Pancreatic Lipase in High Fat-Fed Mice

2018 ◽  
Vol 19 (3) ◽  
pp. 857 ◽  
Author(s):  
Kyunghwa Baek ◽  
Danbi Park ◽  
Hyo Hwang ◽  
Seong-Gon Kim ◽  
Heesu Lee ◽  
...  
1998 ◽  
Vol 273 (47) ◽  
pp. 31215-31221 ◽  
Author(s):  
Mark E. Lowe ◽  
Mark H. Kaplan ◽  
Laurie Jackson-Grusby ◽  
Dymphna D’Agostino ◽  
Michael J. Grusby

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fangjun Yu ◽  
Zhigang Wang ◽  
Tianpeng Zhang ◽  
Xun Chen ◽  
Haiman Xu ◽  
...  

AbstractThe role of intestine clock in energy homeostasis remains elusive. Here we show that mice with Bmal1 specifically deleted in the intestine (Bmal1iKO mice) have a normal phenotype on a chow diet. However, on a high-fat diet (HFD), Bmal1iKO mice are protected against development of obesity and related abnormalities such as hyperlipidemia and fatty livers. These metabolic phenotypes are attributed to impaired lipid resynthesis in the intestine and reduced fat secretion. Consistently, wild-type mice fed a HFD during nighttime (with a lower BMAL1 expression) show alleviated obesity compared to mice fed ad libitum. Mechanistic studies uncover that BMAL1 transactivates the Dgat2 gene (encoding the triacylglycerol synthesis enzyme DGAT2) via direct binding to an E-box in the promoter, thereby promoting dietary fat absorption. Supporting these findings, intestinal deficiency of Rev-erbα, a known BMAL1 repressor, enhances dietary fat absorption and exacerbates HFD-induced obesity and comorbidities. Moreover, small-molecule targeting of REV-ERBα/BMAL1 by SR9009 ameliorates HFD-induced obesity in mice. Altogether, intestine clock functions as an accelerator in dietary fat absorption and targeting intestinal BMAL1 may be a promising approach for management of metabolic diseases induced by excess fat intake.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Gyo-Nam Kim ◽  
Mi-Rae Shin ◽  
Sung Ho Shin ◽  
Ah Reum Lee ◽  
Joo Young Lee ◽  
...  

Pancreatic lipase is the enzyme responsible for digestion and absorption of triglycerides, being its inhibition one of the widest studied methods used to determine the potential activity of natural products to inhibit dietary fat absorption. Decrease of energy intake from dietary fat through inhibition of this enzyme may be an excellent strategy to prevent and treat obesity. The inhibitory activity on pancreatic lipase enzyme ofDiospyros kakifruit andCitrus unshiupeel mixture extract (PCM) was evaluatedin vitroand its antiobesity effects were studied based on the serum lipid parameters analysis from high-fat diet- (HFD-) fed micein vivo. PCM was orally administered at a dose of 50 and 200 mg/kg body weight for 6 weeks. In addition, the activity of pancreatic lipase was assessed using orlistat (positive control). PCM exhibited inhibitory effect on lipase activity with IC50value of 507.01 μg/mL. Moreover, serum triacylglycerol, total cholesterol levels, and visceral fat weight were significantly reduced compared to HFD control mice in PCM 200 mg/kg-treated mice (p<0.05). These results suggest that PCM administration may be a novel potential antiobesity agent for reduction of fat absorption via inhibition of pancreatic lipase.


1990 ◽  
Vol 258 (1) ◽  
pp. G38-G44 ◽  
Author(s):  
C. A. Flores ◽  
P. M. Brannon ◽  
M. A. Wells ◽  
M. Morrill ◽  
O. Koldovsky

To determine the effect of altered dietary fat intake on the rate of fat absorption in the intact animal, we fed male weanling rats either a high fat-low carbohydrate (HF-LC) (calories: 67% fat, 10% carbohydrate, 20% protein) or low fat-high carbohydrate (LF-HC) (calories: 10% fat, 67% carbohydrate, 20% protein) diet for 8 days. Absorption of [14C]triolein was estimated by determining 1) 14CO2 expiration in breath, 2) intestinal triglyceride output using Triton WR-1339, an inhibitor of lipoprotein lipase, and 3) quantitating the disappearance of labeled triolein from the gastrointestinal tract. Changes in the activity of pancreatic lipase and amylase confirmed the adaptation to altered fat and carbohydrate intake. Animals fed the HF-LC diet exhibited approximately twofold greater triolein disappearance, oxidation, and intestinal triglyceride output compared with animals fed LF-HC. There was also a highly significant linear relationship between 14CO2 excretion and intestinal triglyceride output in both diet groups. These data show that high dietary fat content markedly enhances in vivo fat absorption in the weanling rat.


2000 ◽  
Vol 14 (13) ◽  
pp. 2040-2046 ◽  
Author(s):  
Galya Vassileva ◽  
Leslie Huwyler ◽  
Kevin Poirier ◽  
Luis B. Agellon ◽  
Matthew J. Toth

2021 ◽  
Vol 12 ◽  
Author(s):  
David W. McMillan ◽  
Gregory C. Henderson ◽  
Mark S. Nash ◽  
Kevin A. Jacobs

Spinal cord injury (SCI) results in disordered fat metabolism. Autonomic decentralization might contribute to dyslipidemia in SCI, in part by influencing the uptake of dietary fats through the gut-lymph complex. However, the neurogenic contributions to dietary fat metabolism are unknown in this population. We present a subset of results from an ongoing registered clinical trial (NCT03691532) related to dietary fat absorption. We fed a standardized (20 kcal⋅kgFFM–1) liquid meal tolerance test (50% carb, 35% fat, and 15% protein) that contained stable isotope lipid tracer (5 mg⋅kgFFM–1 [U-13C]palmitate) to persons with and without motor complete thoracic SCI. Blood samples were collected at six postprandial time points over 400 min. Changes in dietary fatty acid incorporated into the triacylglycerol (TAG) pool (“exogenous TAG”) were used as a marker of dietary fat absorption. This biomarker showed that those with paraplegia had a lower amplitude than non-injured participants at Post240 (52.4 ± 11.0 vs. 77.5 ± 16.0 μM), although this failed to reach statistical significance (p = 0.328). However, group differences in the time course of absorption were notable. The injury level was also strongly correlated with time-to-peak exogenous TAG concentration (r = −0.806, p = 0.012), with higher injuries resulting in a slower rise in exogenous TAG. This time course documenting exogenous TAG change is the first to show a potential neurogenic alteration in SCI dietary fat absorption.


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