ATF4 deficiency protects mice from high-carbohydrate-diet-induced liver steatosis

2011 ◽  
Vol 438 (2) ◽  
pp. 283-289 ◽  
Author(s):  
Houkai Li ◽  
Qingshu Meng ◽  
Fei Xiao ◽  
Shanghai Chen ◽  
Ying Du ◽  
...  

Chronic feeding of HCD (high-carbohydrate diet) is one of the major contributors to the prevailing of metabolic diseases. ATF4 (activating transcription factor 4) has been shown to play an important role in the regulation of glucose metabolism and obesity development; however, it is unclear how ATF4−/− mice respond to HCD. In the present study, we show that 8 weeks of HCD results in significant higher accumulation of TAGs (triacylglycerols) in livers and impairment in glucose tolerance in ATF4+/+ mice, but not in ATF4−/− mice, compared with those on a normal diet. Meanwhile, energy expenditure is further enhanced by HCD in ATF4−/− mice. Moreover, we show that ATF4 deficiency suppresses HCD-induced SCD1 (stearoyl-CoA desaturase 1) expression, furthermore, oral supplementation of the main product of SCD1 oleate (18:1) increases TAG accumulation in livers of ATF4−/− mice. Taken together, these results suggest that ATF4 deficiency is protective for HCD-induced hepatic steatosis and impairment of glucose tolerance and insulin sensitivity. Furthermore, the resistance to hepatic steatosis is at least in part due to suppression of SCD1 expression under HCD.

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1638
Author(s):  
Ju-Hyoung Park ◽  
Eun-Kyung Ahn ◽  
Min Hee Hwang ◽  
Young Jin Park ◽  
Young-Rak Cho ◽  
...  

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia—a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.


1971 ◽  
Vol 124 (2) ◽  
pp. 283-288 ◽  
Author(s):  
P. F. Swann ◽  
A. E. M. McLean

1. Rats fed on a protein-free high-carbohydrate diet for 7 days metabolized dimethylnitrosamine at only 55% the rate of rats fed on a commercial diet. 2. Dimethylnitrosamine was metabolized by liver slices from rats fed on the protein-free diet at less than half the rate attained by slices from rats fed on a commercial diet. But kidney slices from these rats metabolized dimethylnitrosamine at the same rate as kidney slices from rats on a commercial diet. 3. Methylation by dimethylnitrosamine (70mg/kg body wt.) of N-7 of guanine of the liver RNA and DNA of rats fed on a protein-free diet was only slightly higher than in rats fed on a normal diet given 27mg/kg body wt. In contrast, the methylation by dimethylnitrosamine of guanine in kidney nucleic acids of these rats was three times that in the rats fed on a normal diet. 4. In rats fed on a protein-free diet the incidence of kidney tumours produced by a single dose of dimethylnitrosamine is increased.


2013 ◽  
Vol 144 (5) ◽  
pp. S-909
Author(s):  
Tetsuya Sujishi ◽  
Shinya Fukunishi ◽  
Hideko Ohama ◽  
Yusuke Tsuchimoto ◽  
Akira Asai ◽  
...  

2021 ◽  
Vol 20 (3) ◽  
pp. 6-12
Author(s):  
J. G. Birulina ◽  
V. V. Ivanov ◽  
E. E. Buyko ◽  
O. A. Trubacheva ◽  
I. V. Petrova ◽  
...  

Aim. To study the effects of a high-fat, high-carbohydrate diet on erythrocytes and platelets of rats.Materials and methods. Male Wistar rats (n = 23) were used for the study. The rats were divided into a control group and an experimental group. The rats from the control group were fed with standard rat chow. The rats from the experimental group had received a high-fat and high-carbohydrate diet for 12 weeks. In the rats, body weight and blood pressure (BP) were measured, an oral glucose tolerance test was carried out, and hematological and lipid metabolism parameters were analyzed. The conductance of erythrocyte KCa-channels was measured by the potentiometric method, and platelet aggregation was determined by the turbidimetric method.Results. Feeding the rats with a high-fat, high-carbohydrate diet for 12 weeks resulted in obesity, BP elevation, hyperglycemia, impaired glucose tolerance, and dyslipidemia with pronounced triglyceridemia. In the experimental group, a rise in the number of leukocytes, mainly due to granulocytes, and an increase in the number of platelets and their collagen-induced aggregation were observed. The red blood cell count in the rats of the experimental group did not significantly differ from that of the control group. In the experimental group, multidirectional changes in the membrane potential were observed in response to the stimulation of the KCa-channels in the erythrocyte membrane with the Ca2+ ionophore A23187 or artificial redox systems.Conclusion. The obtained data indicate that a high-fat, high-carbohydrate diet leads to metabolic and hemorheological disorders that are typical of metabolic syndrome.


2002 ◽  
Vol 57 (3) ◽  
pp. 163-170 ◽  
Author(s):  
Nobuyuki Komiyama ◽  
Takashi Kaneko ◽  
Akio Sato ◽  
Wataru Sato ◽  
Kaoru Asami ◽  
...  

2002 ◽  
Vol 12 (4) ◽  
pp. 480-489
Author(s):  
Mark H. Roltsch ◽  
Judith A. Flohr ◽  
Patricia B. Brevard

The purpose of this study was to examine the metabolic consequences of a moderate variation in dietary fat content of male endurance athletes during submaximal exercise. Six males (age, 29.8 ± 11 years; weight, 72.3 ± 10 kg) · with an average maximum oxygen uptake (V̇O2max) of 66 ± 10 ml/kg/min were tested on their normal diet and 3 experimental diets. The energy contributions from protein, carbohydrates, and fats were 16/59/22 (3% alcohol), 14/53/33, 13/72/15, and 16/61/23% for the normal diet (N), fat supplemented diet (F), high carbohydrate diet (C), and adjusted normal diet (AN), respectively. The F diet was designed to significantly increase fat content compared to the normal diet and be easily maintained by the athletes. Caloric content of the F, C, and AN diets were adjusted to meet estimated total daily energy expenditure. The difference between the N and AN diets is that the AN has been adjusted to meet estimated total daily energy expenditure. The diets were randomly assigned after substrate utilization testing on the N diet and were consumed for 7 days prior to testing. Substrate utilization was recorded at steady state (73 ± 1.4% of V̇O2max) while running on a treadmill for 40 min. There were no significant differences in respiratory exchange ratio between any of the dietary manipulations. No significant differences were observed for lactate, V̇O2, or HR during submaximal testing on the N, F, C, and AN diets. These data indicate that a fat supplemented diet did not affect substrate utilization during 40 min of steady-state submaximal exercise when compared to a high carbohydrate diet or the participant’s normal and adjusted normal diets.


2013 ◽  
Vol 32 ◽  
pp. S23
Author(s):  
M. Soeters ◽  
M. Schooneman ◽  
F. Vaz ◽  
C. Hollak ◽  
S. Houten

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