I can lose weight without eating, can I have such a good thing?

We all know that obesity is not only related to the usual eating habits and lifestyle, but also has a great relationship with genes. Being overweight not only causes inferiority in appearance, but also has serious health consequences, such as cardiovascular disease (mainly heart disease and stroke), type 2 diabetes, musculoskeletal diseases such as osteoarthritis, and some cancers (endometrial lining). cancer, breast and colon cancer), etc.

(Image source: 123RF)

High-calorie foods are delicious and tempting, and exercise is difficult and tiring. Why are some people born with a "skinny physique"? Is there a way to eat with confidence and not gain weight?

Two recent studies published in the journals Cell and Science Advances suggest that gene therapy may help people maintain their ideal weight without dieting and even build muscle strength.

Cancer gene linked to obesity

I believe that from childhood to adulthood, there will be people around you like this: some people eat a lot without exercising, but they are not very fat, and some people seem to drink cold water and gain weight.

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Previous studies on obesity have found that there are several genes in the human body that are susceptible to obesity, but most of the studies are from the perspective of obesity, and few studies have explored the genetics of body weight loss.

Recently, "Cell" magazine published important research results made by the team of Josef M. Penninger of the Australian Academy of Sciences and the team of Nele Gheldof and Jorg Hager of the Nestle Institute of Health Sciences in Switzerland.

The research team found that ALK expressed in hypothalamic neurons can regulate fat breakdown through sympathetic nerves. After knocking out the ALK gene, even if the mice were fed a high-fat diet for a long time, they still did not gain weight. The researchers believe that their study shows that the oncogene ALK is a "skinny gene."

(Summary of the research process | Source: Cell)

The Chinese name of ALK is anaplastic lymphoma kinase. It was first discovered because of overactivation of rearrangement with other genes, leading to the occurrence of tumors. ALK rearrangement is currently an important target for the treatment of cancer, and related drugs have been put into clinical use.

In experiments on mice, MRI analysis showed that the ALK-deficient mice had normal lean mass, but had significantly less fat and smaller fat cells than normal mice. However, there was no difference in food intake between the deficient and normal mice, and there was no difference in the absorption of nutrients in the gut.

Although this study has proved that ALK is a slimming gene from multiple perspectives, this test is still in the basic stage and is still far from clinical application. Penninger said they will continue to study whether ALK-targeting inhibitors have weight loss effects.

Obesity as a risk factor for osteoarthritis

Osteoarthritis (OA) is a degenerative disease characterized by degenerative damage to cartilage and reactive hyperplasia of the joint margins and subchondral bone, and despite its prevalence and impact, there is currently no treatment for osteoarthritis. Relief medication.

Exercise and weight loss are often the primary interventions for osteoarthritis, but multiple studies have shown that long-term weight loss and increased muscle strength can be difficult for overweight older adults.

(Image source: 123RF)

A new type of gene therapy can be used without extra exercise, according to a new study published in the journal Science Advances, led by a team of researchers at Washington University (St. Louis) School of Medicine. Prevents obesity and helps build muscle in mice fed a high-fat diet.

Previous studies have shown that obesity and dietary fatty acids (FAS) play an important role in the development of osteoarthritis, and obesity caused by metabolic dysfunction is likely to be a major risk factor for osteoarthritis.

In addition, both obesity and osteoarthritis are associated with loss of muscle integrity and strength, and although the mechanisms between obesity, osteoarthritis, and muscle are not fully understood, strategies focused on muscle protection and reduction of metabolic inflammation may lead to Provide a more attractive direction for the treatment of osteoarthritis.

(Image source: 123RF)

"Obesity is the most common risk factor for osteoarthritis, and being overweight can hinder a person's ability to exercise and prevent patients from fully benefiting from physical therapy," explained Farshid Guilak, the study's senior researcher.

"Here we found a way to rapidly build muscle using gene therapy," Guilak said. "It had profound effects in mice and controlled their body weight, suggesting that a similar approach may be effective in arthritis, especially in morbid obesity."

FST gene therapy may increase muscle mass

The study used the gene therapy of follistatin (FST), a protein expressed in nearly all animal tissues that was first discovered and described in the late 1980s. Originally researched to explore its role as a reproductive hormone, follistatin was later found to affect a range of cellular processes, including muscle growth, while suppressing inflammation.

Previous animal studies have shown that gene therapy that increases follistatin expression can combat certain degenerative muscle diseases. The new study examines whether the therapy could help treat osteoarthritis by increasing muscle mass and reducing metabolic inflammation associated with obesity.

(Image source: Science Advances)

(Effect of AAV-FST gene therapy on muscle structure and function)

During the experiment, the researchers gave each 8-week-old mouse a single injection of a virus that carries the gene for follistatin, which blocks the activity of a protein in the muscles, thereby preventing muscle growth. This allowed the mice to gain significant muscle mass without having to do more exercise than usual.

The trial found that even without additional exercise, these "super mice" more than doubled their muscle mass and nearly doubled their strength while continuing to eat a high-fat diet. These "super mice" had less cartilage damage, fewer metabolic problems and healthier hearts and blood vessels than other littermates that did not receive gene therapy.

(Image source: medicalxpress)

Like the ALK gene study above, follistatin gene therapy still needs long-term studies to prove its safety, but this therapy provides a new direction for the treatment of diseases such as obesity and muscular dystrophy.

In short, no matter what kind of obesity gene experiment it is, it is still in a very early stage, and we can look forward to future research applications, but at present, a reasonable diet and moderate exercise are still required (if you want to know how to lose weight scientifically, click here), especially for non-"easy" Those who are "lean physique" should control their weight and stick to a healthy lifestyle.

Editor: Dr. Chunyu

references:

[1]Ruhang Tang,Natalia S. Harasymowicz,Chia-Lung Wu,et al.,Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet–induced obesity,Science Advances 08 May 2020:Vol. 6, no. 19, eaaz7492,DOI: 10.1126/sciadv.aaz7492

[2]M. Nakatani, Y. Takehara, H. Sugino, M. Matsumoto, O. Hashimoto, Y. Hasegawa, T. Murakami, A. Uezumi, S. Takeda, S. Noji, Y. Sunada, K. Tsuchida, Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice. FASEB J. 22, 477–487 (2007).

[3]Zheng H, Chen C. Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies[J]. BMJ Open. 2015 Dec 11;5(12):e007568. doi: 10.1136/bmjopen-2014-007568.

[4]Michael Orthofer ,Armand Valsesia ,Reedik M?gi,et al.,Identification of ALK in Thinness,Published:May 21, 2020DOI:https://doi.org/10.1016/j.cell.2020.04.034