Past life obesity gene

Obesity is not a single gene determines the quality of genetic traits, but more genetically determined number of genetic traits. From ob to db then FTO, but also whether it is now or in the future, any obesity gene discovery is not the last, and each found an obesity gene, may provide new molecular targets for drugs to lose weight. The obesity gene discovered what the story behind it? This article will take you into the bizarre world of the obesity gene, so you suddenly cerebral hole wide open.
 Physiological basis of obesity is the catabolism of fat synthesis rate of its metabolic rate, and fat decomposition and synthesis of a series of enzymes involved in the catalysis, uptake, transport and distribution of fat synthetic precursor of glycerol and fatty acids also affect the decomposition of fat and synthesis, fat accumulation and consumption is also affected by nerve - regulate hormone secretion and other factors. Therefore, obesity must be a trait controlled by multiple genes (quantitative genetics), rather than one controlled by a single gene traits (genetic quality). Up till 2006, obesity-related genes have been found to have up to 41.
Since obesity trait controlled by the gene, then there must be a significant obesity familial genetic predisposition. The genetic influence on BMI varies race varies, ranging from 6 percent share to 85 percent. Fat chance fat woman gave birth to parents of up to 80%, while giving birth parents the opportunity to lean fat woman is only 10%. If the parents a fat one thin, obese children opportunities seem very high, such as Hong Kong late actress "fat" (Lydia) fat, her husband, "Adam" (Adam) was relatively thin, but their only child Joyce weight reached 180 pounds. According to statistics, carry double copies of FTO gene, with an average weight increase of 3 to 4 kg, 1.67-fold increased risk of obesity.
--ob And db first obesity gene discovered
Early in the 1950s found under non-obese mouse strain capable of producing to obesity (obesity) in front of the gene in obese offspring of two phenomena, and has proved to fat mice carrying two mutant allele homozygotes (ob / ob), letter name. Until the 1990s, ob gene was only located in the exact position on the chromosome, and ultimately identify the gene encoding the product of OB is leptin. Leptin synthesis in adipose tissue and secreted into the bloodstream, via the blood circulation to the brain, through a combination of leptin receptor in the hypothalamus convey gastrointestinal satiety signal, then reduce consumption. This means heterozygotes carrying OB / OB gene homozygous dominant or Ob / ob gene can customize the control of food intake and maintain normal weight, while carrying ob / ob homozygous recessive gene does not feel satiety signal They will not stop eating, leading to nutritional excess weight gain.
Human genome only a single copy of the OB gene, but can also be mutated. Ob mutant gene first found in 1997, until January 2015, it has been found a total of eight different ob mutant gene carriers in its infancy, excessive appetite was diagnosed with extreme obesity. The United States ratified in 2014 will be used to improve congenital leptin deficiency and leptin general lipodystrophy. As a lipid-lowering drug leptin analogue metreleptin (trade name Myalept), was in 2013 and 2014 respectively in Japan and the United States was approved by the market.
1960 also found with the ob / ob mice were equally obese and suffering from diabetes in mice, but they carry the mutation of two copies of different genes, so the word to diabetes (diabetes) and the two-letter name of the gene (db / db). With the discovery of the leptin gene, and finally confirmed DB gene coding for the leptin receptor gene in 1995. Carry db / db homozygous recessive gene has been used as obesity, diabetes and dyslipidemia animal model, despite its hypothalamic leptin receptors, but no activity can not convey the fullness signal induced leptin The results are the same as leptin mutations cause genetic obesity. Interestingly, the obese mice can be activated by swimming uncoupling protein expression, and promote fat burning, play a role in weight loss.
The most complex obesity gene --FTO
It is said that FTO gene derived from the name (fatso) the term "big fat boy" abbreviated, because the gene is 1999 from mouse "convergence toe" (fused toes) of a mutant clone of up to hundreds of thousands of base based on the sector. However, FTO is also considered fat mass and obesity-associated protein (lipids and obesity-related protein) acronym. This differs from the study is that obesity gene function, it is first conducted association studies of obesity in humans rather than animals, and it is currently the most complex mechanism, but there have been new discoveries of the obesity gene.
年 2007, FTO obesity gene was first identified as a risk gene in European populations. Carrying a single copy of the FTO gene were on average 1.2 kg weight gain, carry copies of the FTO gene were double the average weight gain of 3 kg, and 1.67 times increased risk of obesity. In recent years, there have been many studies have shown, FTO gene first segment non-coding sequences (introns) have 10 single nucleotide polymorphisms risks associated with obesity, one of which is called rs9939609 single nucleotide acid sequence polymorphisms in the population of Western Europe and Central Europe accounted for 45%, the proportion of indigenous people in the West African Yoruba of up to 52%, the proportion of Chinese people in East Asia and the Japanese also have 14%.
2014 "Nature" magazine reported that non-coding sequences FTO gene may interact with the control and development of homeobox gene promoter IRX3 occurred IRX3 gene expression in the brain, so that the consumption of fat in brown adipose tissue into fat storage white adipose tissue. IRX3 deficient mice again white adipose tissue into brown adipose tissue, its weight can be reduced by 25% to 30%. Not long ago, "New England Journal of Medicine," published in the latest paper pointed out, FTO gene non-coding region single nucleotide polymorphism rs1421085 sequence in a different base, you can decide mice are fat or thin, its mechanism is through the impact ARID5B repressor binding on the degree of enhancement son, so IRX3 and IRX5 expressed or not expressed in early adipocyte differentiation.
Specifically, if the zone FTO become thymine cytosine, then ARID5B repressor can not bind enhancer, IRX3 and IRX5 expression, FTO is the "fat" genes, mitochondria produce thermal effects reduce 1/5. In contrast, when cytosine is substituted thymine, ARID5B repressor can be combined with an enhancer, IRX3 and IRX5 not express, FTO become "thin" genes, mitochondria increased thermogenic effect 1/7. If the mouse fat cells inhibit expression IRX3 neither change nor appetite, increased physical activity can achieve rapid weight loss goals.
Amino acid sequence alignment, with an alkylating found FTO homologous protein B, while the latter function is DNA demethylation. New research shows that, FTO can make RNA in the 6-methyl adenine oxidative demethylation, but it is unclear whether FTO influence fat metabolism by altering epigenetic modification status, pending further study.
The most relevant of obesity gene
After removal of the signal before MSH MSH peptide produced the original, it former hormone-converting enzyme 1 effect is cut, respectively, to produce α- melanocyte stimulating hormone, adrenocorticotropic hormone, β- endorphin and armor methionine enkephalin, which α- melanocyte stimulating hormone important for appetite regulation. MSH receptor binding ago MSH derived α- melanocyte stimulating hormone after, can play a physiological effect of appetite regulation. 2008 first reported the MSH receptor gene mutations in human genetic obesity and found that it makes the body mass index of 30 or more prevalence of 1.0% to 1.5%. Before hormone-converting enzyme 1 gene associated with obesity have been elucidated in 2009, while the former MSH genes associated with obesity until 2012 was only finalized.
While we have found many obesity-related genes, but they just increase the susceptibility to obesity, it does not mean that obesity gene carriers will inevitably gain weight, because obesity also relies role in the formation of environmental factors. Of course, carrying human obesity gene, which is more difficult to control weight, weight loss drugs are the most urgent expectations. However, even if the mechanism of FTO gene is clarified, it will not be like the media boasted that, in the future as long as the injection of a needle "genetic medicine", can be completely cured of obesity.
First, it is impossible to agree fine egg gene editing, the "fat gene" transformed into a "lean gene", which gave birth to a "thin doll." Secondly, it is impossible for scientists obese baby or each adult fat cells genetically modified in order to achieve true "gene lose weight." The most realistic possibility is that obesity genes, such as for deficient ob or db, can add artificial leptin or leptin receptor alleviate the condition by injection. As a variety of obesity gene expression, the future dedicated to finding targeted inhibitors and to develop new weight-loss drug is promising.

 Academy of Sciences Computer Network Information Center