What is the decision between grace and temperature?

A breeze seems to blow into the bones, making people tremble. As the weather gets colder and colder, people's clothes get thicker and thicker, but you can't have grace and temperature at the same time. The more you cross, the more bloated you look. Some beauty lovers choose to show their ankles and necks in order to show fashion, but this way of dressing is harmful to health. Do you really have to choose between grace and temperature?

A study published in the American Journal of Human Genetics shows that the deletion of α -actin 3 can improve human cold tolerance by increasing muscle tension. Loss of function (LOF) mutation of ACTN3 gene will lead to the deletion of α -actin 3. This gene variant that affects skeletal muscle function may have protected human beings from low temperature when they migrated from Africa to Europe more than 50,000 years ago. With modern human beings migrating to colder environments, this variant has become more common.

About1500 million people in the world carry ACTN3 LOF variants, so they lack α -actin 3 (human α -actin 3 is encoded by ACTN3 gene). Scientists believe that the loss of α -actin 3 will reduce the number of fast muscles. Skeletal muscle consists of long cylindrical cells called muscle fibers. There are two types of muscle fibers, slow muscle fibers or muscle contraction (type I) and fast muscle fibers (type II). Slow muscle fibers use oxygen more effectively to generate energy, while fast muscle fibers are less efficient. However, fast muscle fibers emit faster, which makes them generate more power than slow muscle fibers (type I). Fast muscle fiber and slow muscle fiber are also called white muscle fiber and red muscle fiber respectively.

A summary of the potential extensive influence of ACTN3 genotype on sports performance

With the human migration to cold climate, the variation of LOF has become more and more abundant, and researchers suspect that LOF may play a role in improving cold tolerance. To test this idea, the researchers conducted experiments on humans and mice respectively.

mankind

Forty-two healthy male adults aged 18 ~ 40 were recruited, and their physical activity momentum was moderate (weekly physical exercise time

Physical characteristics and baseline body temperature of individuals in RR group and XX group.

Subjects, whether lacking α -actin 3(XX) or having ACTN3(RR), were soaked in water at 65438 04℃ for 20 minutes, stopped in room temperature air for 65438 00 minutes, and then continued to soak in cold water until the rectal temperature reached 35.5℃, or the total * * * lasted for 65438 020 minutes. During the whole cold water exposure, the proportion of individuals in XX group (69%) who could keep their body temperature above 35.5℃ was significantly higher than that in RR group (30%). On average, the loss of α -actin 3 will cause the body temperature of rectum and calf muscles to drop by half.

Temperature measurement and physiological reaction during cold water immersion

mouse

In the acute temperature exposure experiment, WT female mice and ACTN3 KO mice aged 12 weeks were kept in cages at 30℃ or 4℃ respectively. Simply put, before the experiment, the mice were placed in a heat-neutral (30℃) environment and adapted to this temperature for 20 hours (free to eat water and food). Mice exposed to low temperature took out food, water and bedding within 5 hours.

Within 5 hours from 8:00 to 14:00, the core body temperature was measured with a rectal probe (BAT- 12 microprobe thermometer). The body temperature was measured at 0, 30, 60, 90, 120, 180, 240 and 300 minutes. The weight was recorded before and after the 5-hour temperature measurement.

In mice, ACTN3 knockout (KO) led to the change of intracellular Ca2+ treatment, and the leakage of SR Ca2+ increased significantly. Then, the Ca2+ of the thermally active sarcoplasmic reticulum (SR, a special endoplasmic reticulum in myocardial and skeletal muscle cells, whose function is to participate in muscle contraction) is regenerated by SERCA. The decoupling of SERCA activity and actual Ca 2+ transport to SR is considered to be the key factors of muscle non-trembling thermogenesis.

SERCA is expressed in several different subtypes in mammalian tissues. SERCA 1 and SERCA2a are the main subtypes of adult fast muscle fibers and slow muscle fibers respectively. Notably, the researchers detected the dominant transfer of SERCA 1 in RR muscle to SERCA2a in XX muscle (Figures A and B). SR Ca2+ storage protein CSQ also showed fiber type-dependent subtype distribution. CSQ 1 is dominant in fast muscle fibers, and CSQ2 is dominant in slow muscle fibers. The researchers observed that the total expression of CSQ in XX and RR muscles was similar, while the expression of CSQ2 in XX was about twice that in RR muscles (Figures C and D).

ACTN3 deficiency is accompanied by the transition to slow skeletal muscle phenotype.

In addition, LOF carriers also showed a transfer to slow muscle fibers, which led to an increase in muscle tension, instead of generating heat through trembling during cold water immersion. In contrast, individuals with ACTN3 function have more fast muscle fibers, which doubles the speed of high-intensity explosive activities. The superior cold tolerance of LOF carriers is not accompanied by the increase of energy consumption, which shows that the continuous low-intensity activation of slow muscle fibers is an effective way to generate heat. Other results in mice showed that the lack of α -actin 3 did not increase the heat production of brown adipose tissue in hibernating mammals and human infants.

Brazaitis, the author of the study, said: "Although people who lack α-actin 3 can generate heat efficiently, which was originally their advantage when they turned to a colder climate, in modern society, this may actually be unfavorable. In modern society, housing and clothes make cold prevention less important, and we can basically get food indefinitely. Such energy efficiency will bring problems, leading to obesity, type 2 diabetes and other metabolic diseases. "

In a word, people who lack α -actin 3 show better cold tolerance during cold water immersion. These findings provide a mechanism for the increase of X allele frequency when modern humans migrated from Africa to Central and Northern Europe with colder climate more than 50,000 years ago.