Guangzhou Health Center has bred a model of pigs who are congenitally obese but free from diabetes

Obesity is known to be a significant risk factor
for type 2 diabetes.
However, among Samoa, Māori and other populations, obesity rates are among the highest in the world, but type 2 diabetes
is rare.
The investigation found that these obese people carried a unique CREB 3 regulatory factor gene variant, known as CREBRFR457Q
.
Cultivating experimental animal models that can simulate phenotypic similarities and elucidating the mechanism behind them will provide effective targets for the development of drugs that reduce the risk of diabetes in obese people
.
Foreign scholars have established a mouse model with human CREBRFR457Q homologous mutation, but the mouse model does not show the obese phenotype, metabolism-related indicators abnormalities and protective effect on
type 2 diabetes.
Since porcine lipid metabolism and islet structure are more similar to humans, CREBRFR457Q was successfully cultivated using gene editing and somatic cell cloning technology Point mutant pig model and obtain fertile offspring
.

CREBRFR457Q mutant pigs showed an obese phenotype, their weight, abdominal circumference and overall fat content were higher than those of wild pigs, and fat accumulation was mainly subcutaneous, and visceral fat accumulation was not significant
.
Compared with wild-type adipose tissue, point mutant pig adipocytes have a large number and small
size.
In vitro adipose differentiation experiments have also shown that the CREBRFR457Q variant promotes preadipocyte differentiation
.
Obesity caused by CREBRF R457Q is caused by an increase in the number of fat cells (hyperplasia) rather than an increase in volume (excessive enlargement), and obesity caused by mutations in CREBRFR457Q is to some extent protective obesity
.
Blood biochemical analysis showed that this point mutation upregulated insulin levels
in the blood while maintaining normal insulin sensitivity.
Through the monitoring of oxidation level, the research group found that this point mutation can reduce the oxidative metabolism capacity of adipose tissue, enhance antioxidant capacity, reduce the production of ROS, thereby reducing the level of oxidative stress, and thus the result Reactions such as insulin resistance
.
This study preliminarily revealed the mechanism by which this point mutation leads to obesity by promoting adipoiesis, and reduces the risk of type 2 diabetes by reducing oxidative metabolism and maintaining normal insulin sensitivity, which provides a new idea
for the prevention of diabetes in obese people.

The co-corresponding authors of the paper are Associate Researcher Fan Nana and Researcher
Wu Donghai of Guangzhou Health Institute.
Li Yingying, Chen Huangyao, postdoctoral fellow Wang Hai, doctoral students of Guangzhou Health Institute, and Liao Yuan, a master student jointly trained by Guangzhou Health Center and Anhui University, are the co-first authors
.
The research was supported
by Guangdong Science and Technology Program, National Key R&D Program, Chinese Academy of Sciences Pilot Program, Guangzhou Science and Technology Plan and other projects.