scholarly journals Biphasic Production of Anti-ApoB100 Autoantibodies in Obese Humans and Mice

2021 ◽  
Vol 14 (4) ◽  
pp. 330
Author(s):  
Moon Kyung Choe ◽  
Hyung-Ji Kim ◽  
Nan Hee Kim ◽  
Bert Binas ◽  
Hyo Joon Kim

Obesity is associated with autoimmunity, a phenomenon considered as harmful. Here we show that obese mice and humans produce IgG-type autoantibodies that specifically recognize apolipoprotein B-100 (ApoB100), its native epitope p210, and the synthetic p210 mimotope pB1. By contrast, antibodies against epitopes p45 and p240, which have been associated with atherosclerosis, were not detected in either the humans or mice. In a longitudinal analysis of high fat diet-fed mice, autoantibody production rose with increasing body weight, then decreased and plateaued at morbid obesity. Likewise, in a cross-sectional analysis of sera from 148 human volunteers spanning a wide BMI range and free of comorbidities, the immunoreactivity increased and then decreased with increasing BMI. Thus, the obesity-related ApoB100-specific natural autoantibodies characteristically showed the same epitope recognition, IgG-type, and biphasic serum levels in humans and mice. We previously reported that a pB1-based vaccine induces similar antibodies and can prevent obesity in mice. Therefore, our present results suggest that autoantibodies directed against native ApoB100 may mitigate obesity, and that the vaccination approach may be effective in humans.

2015 ◽  
Vol 35 (6) ◽  
pp. 2349-2359 ◽  
Author(s):  
Youli Xi ◽  
Miaozong Wu ◽  
Hongxia Li ◽  
Siqi Dong ◽  
Erfei Luo ◽  
...  

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.


2014 ◽  
Vol 9 ◽  
pp. 211-224 ◽  
Author(s):  
Jihang Chen ◽  
Hoi Shan Wong ◽  
Hoi Yan Leung ◽  
Pou Kuan Leong ◽  
Wing Man Chan ◽  
...  

2022 ◽  
Author(s):  
Somayeh Aslani ◽  
Saman Bahrambeigi ◽  
Davoud Sanajou

Despite dietary/lifestyle modifications as well as glycemic and lipid control, non-alcoholic fatty liver disease (NAFLD) imposes a considerable risk to the patients by advancing to non-alcoholic steatohepatitis (NASH). The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor for advanced glycation end products (RAGE), against circulating indices of liver injury in high fat diet-induced diabetic mice. FPS-ZM1 at 0.5. 1, and 2 mg/kg (orally) was administered for 2 months, starting 4 months after provision of the high-fat diet. Tests for glucose homeostasis, liver injury markers, and hepatic/plasma miR-21 expressions were performed. FPS-ZM1 attenuated diabetes-induced elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), and alpha glutathione-S-transferase (α-GST) as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It also decreased diabetes-associated elevations in serum ferritin and plasma cytokeratin 18 fragments. Additionally, FPS-ZM1 down-regulated elevated expressions of miR-21 in the liver and plasma of diabetic mice. These findings highlight the benefits of FPS-ZM in alleviating liver injury in mice evoked by high-fat diet-induced type 2 diabetes and suggest FPS-ZM1 as a new potential adjunct to the conventional diet/lifestyle modification and glycemic control in diabetics.


2021 ◽  
Author(s):  
Sathish Sivaprakasam ◽  
Sabarish Ramachandran ◽  
Mohd Omar Faruk Sikder ◽  
Yangzom Doma Bhutia ◽  
Mitchell Wachtel ◽  
...  

a-Methyl-L-tryptophan (a-MLT) is currently in use as a tracer in its 11C-labeled form to monitor the health of serotonergic neurons in humans. In the present study, we found this compound to function as an effective weight-loss agent at pharmacological doses in multiple models of obesity in mice. The drug was able to reduce the body weight when given orally in drinking water (1 mg/ml) in three different models of obesity: normal mice on high-fat diet, Slc6a14-null mice on high-fat diet, and ob/ob mice on normal diet. Only the L-enantiomer (a-MLT) was active while the D-enantiomer (a-MDT) had negligible activity. The weight-loss effect was freely reversible, with the weight gain resuming soon after the withdrawal of the drug. All three models of obesity were associated with hyperglycemia, insulin resistance, and hepatic steatosis; a-MLT reversed these features. There was a decrease in food intake in the treatment group. Mice on a high-fat diet showed decreased cholesterol and protein in the serum when treated with a-MLT; there was however no evidence of liver and kidney dysfunction. Plasma amino acid profile indicated a significant decrease in the levels of specific amino acids, including tryptophan; but the levels of arginine were increased. We conclude that a-MLT is an effective, reversible, and orally active drug for the treatment of obesity and metabolic syndrome.


Diabetologia ◽  
2018 ◽  
Vol 61 (9) ◽  
pp. 2030-2042 ◽  
Author(s):  
Steef Kurstjens ◽  
Janna A. van Diepen ◽  
Caro Overmars-Bos ◽  
Wynand Alkema ◽  
René J. M. Bindels ◽  
...  

Author(s):  
Sarmila Nepali ◽  
Do‑Kuk Kim ◽  
Hoon‑Yeon Lee ◽  
Hyeon‑Hui Ki ◽  
Bo‑Ram Kim ◽  
...  

2019 ◽  
Vol 28 (4) ◽  
pp. 1207-1215 ◽  
Author(s):  
Denis Nchang Che ◽  
Hyun Ju Kang ◽  
Byoung Ok Cho ◽  
Jae Young Shin ◽  
Seon Il Jang

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