I have no idea when I bought this book. I didn't remember until I gained three pounds in the Spring Festival recently. I thought it would tell me some tips to lose weight, and I felt cheated. But looking back at the title, people only say that it is biological cultivation, not a secret recipe for losing weight, but there is nothing wrong with it. This is a great popular science book, which has been extended on the basis of high school biology class. Let me see what the concept of rote learning is really useful. From this book, we can know why we are fat. As for how thin we are, the author can only explain some basic life processes, and throwing someone to talk about losing weight is hooliganism. In addition, the contribution of scientists and pharmaceutical companies in the long history of biology mentioned in the book to human anti-obesity is respectable. Although the current foodies still have to "shut up and open their legs", maybe in the near future, we will have external forces to control our appetite. We will eat whenever we want, stop when we are full, and soon we will be hungry, and then we will eat when we are hungry. I have hope for this day.
The four chapters of the book, starting with fat, fully reveal the secret of hyperlipidemia, from normal reaction mechanism to abnormal diseases, and then lead to the process of drug research and development. The last chapter talks about hyperglycemia in the same way. We can see that biologists have been struggling for human health, insisting on a certain phenomenon, having some inspiration, and studying around the clock in the laboratory. Even the pursuit of fame and profit has brought miracles to thousands of people. The author's description in this respect reproduces this scientific research spirit.
The human exploration of obesity originated from two little mice-the sugar mouse and the fat mouse. By connecting two mice with normal mice, scientists discovered leptin and leptin receptor-appetite suppression. Fat mice lack leptin and sugar mice lack receptors, so fat mice become thinner after receiving leptin from normal mice, while sugar mice are still obese, and conjoined mice with it die because they receive more leptin. Several years later, scientists discovered the 2G7 gene that produces leptin through gene linkage, but it was found in human white fat. Therefore, fat has a natural negative feedback, which increases fat-inhibits appetite-and prevents fat from continuing to increase. In addition, white fat will also participate in fat metabolism, inflammatory immunity, vascular hemostasis, angiogenesis, blood pressure, appetite energy balance, nutrient transport, insulin sensitivity and blood glucose homeostasis. What I want to study below is such a good negative feedback. Why am I still fat?
1997 who believes that obesity is a disease. A simple and rude criterion for judging obesity is that the body mass index exceeds 30. For China people with high fat content, 24 are overweight and 28 are obese. Compared with the normal population, the probability of overweight people suffering from heart disease, stroke, type 2 diabetes and some cancers (breast cancer and colorectal cancer) is significantly increased. Gluttony is not only an evolutionary instinct of eating food, but also a pathological neurobiological phenomenon. Well, it's about losing weight. Medical means of losing weight is a great law of conservation of energy. The energy intake is carbohydrates, protein and fat. Energy output is divided into metabolic energy consumption (accounting for 60%), exercise, daily activities and digestive energy consumption. The change of weight is not a simple output-input, but
Weight change = (total energy of food × energy absorbed by human body)-(metabolism+physical consumption+digestion and absorption consumption)
There are five starting points based on energy conservation: 1, reducing the total energy intake of food; 2, reduce the absorption capacity; 3. Increase metabolic consumption; 4. Increase physical activity; 5, increase the consumption of food digestion and absorption. The last item accounts for 10% of the total energy consumption, which has a linear relationship with energy intake and dies silently. High-intensity exercise can change the chemical modification level and physiological activity of hundreds of protein molecules in the body, which is unmatched by any medicine. Then the processing is mainly 1-3.
For the first point, reducing food intake can be achieved through weight-loss surgery or weight-loss drugs. Weight loss surgery: the stomach and small intestine are the most important digestive and absorptive organs of the human body. The stomach is responsible for grinding food, mixing gastric acid and pepsin into food, grinding into food paste, and closely contacting with the small intestine which is several meters long. Nutrient molecules are absorbed into the intestinal wall cells of the small intestine and sent to various organs of the body through the circulatory system to participate in metabolism. Therefore, the means of weight loss surgery is to make the stomach smaller or the small intestine shorter through gastric banding or bypass surgery. But this operation is limited to people, and patients with body fat above 30 can use it. Another method is diet pills. Inspired by leptin, scientists extracted the DNA encoding leptin protein and put it into the bacterial genome for mass reproduction, but the slimming effect was not ideal. In fact, the proportion of patients with leptin deficiency is extremely low, and most of them are obese because of unhealthy lifestyles. Leptin can maintain a basic negative feedback, but it can't control your appetite for food. Although the level of leptin in the body remains high for a long time, the human body reacts slowly to leptin, which is leptin resistance. Leptin resistance can't suppress appetite. At present, some pharmaceutical companies are studying leptin sensitizing drugs, which may fundamentally achieve the effect of losing weight. Drugs to suppress appetite are still being explored. In the early years, it was found that amphetamine made of ephedrine (the raw material of methamphetamine) had the function of losing weight in addition to treating cold and stuffy nose, so chemists took its essence to remove its dross and changed it to Flaaming, but the rebound was serious and there were many side effects. And his wife, Fentrang, and his son, Fenfen, all went to the same fate. Later, scientists found that serotonin, a neurotransmitter controlled by Finn Flaaming, can suppress appetite as long as it can activate serotonin receptor protein, so in 2065438+2002, Chlorcatherine came into being.
For the second point of reducing absorption capacity, the digestion process of the three major energy sources is: protein-amino acid-fuel or protein synthesis; Carbohydrate-sugar-fuel; Fat-fatty acid-fuel. Part of the fuel provides the energy needed for the body to run, and the surplus fuel is stored in the form of fatty acids. By destroying enzymes that digest nutrients, such as amylase, protease, lipase, etc. It inhibits the activity of small intestine, reduces the digestion and absorption function and reduces the energy absorption of the body. Orlistat is the job of tissue lipase to prevent the decomposition and absorption of fat, but it will cause embarrassing problems of excretion (dare not think about it).
For the third point of increasing metabolic consumption, scientists have found that brown fat will burn wildly and consume fat under cold conditions. A drug called Milla perone is an adrenergic receptor activator, which can activate brown fat to work.
Simply put, hyperlipidemia is a disease caused by high fat content in the blood. The blood sample looks terrible and greasy. The fat in blood vessels will slow down the blood flow, and it will deposit on the blood vessel wall, which will hinder the smooth flow of blood. When the deposited fat particles far exceed the immune cells that come to clean up, the latter will burst and die in large numbers, and the fragments will form a layer of protein network fixed fat, even wrapped by a layer of muscle cells. In order to ensure the smooth flow of blood, the muscle of blood vessel wall will expand continuously, which will eventually lead to the deterioration of blood vessel elasticity and atherosclerosis. In addition, vascular plaque with relatively stable structure will affect local blood circulation for a long time, leading to insufficient blood supply; Once the plaque with unstable structure is destroyed, fat molecules and protein will leak out, causing platelet aggregation and coagulation, forming thrombus. If the coronary artery supplying blood to the heart appears sclerosis or thrombosis, it will induce coronary heart disease.
Fat is insoluble in water, and its transportation depends on apolipoprotein. The shell is formed by polymerization of protein molecules and phospholipid molecules, and can hold thousands of fat molecules. From large to small, it can be divided into chyle granules, very low density, medium density, low density and high density lipoprotein. Very low density lipoprotein is responsible for transporting triacylglycerol synthesized by the liver to adipose tissue for storage, while low density lipoprotein and high density lipoprotein are responsible for another fat molecule-cholesterol. Low-density lipoprotein will leak some cholesterol from time to time in blood vessels, which is easy to accumulate into plaques, while high-density lipoprotein can reabsorb cholesterol in blood vessels. Cholesterol is a substance synthesized by bile, which is very important to the digestive system and also participates in the synthesis of various hormones. In addition, cholesterol is one of the most important mosaic substances on the cell membrane, which allows protein molecules on the cell membrane to move freely and achieve extension, folding and throughput. Cholesterol comes from self-synthesis and food acquisition, and the largest cholesterol processing factory in the human body is the liver. Scientists have discovered ——HMG-CoA reductase, the most important destroyer of cholesterol synthesis in skin cells. Low density lipoprotein in blood can bind to the cell surface and inhibit cholesterol synthesis.
Since then, the medical community has begun to increase its firepower. Nicotinic acid (vitamin B3) can reduce cholesterol in human blood and become the first lipid-lowering drug. Cholestyramine promotes the liver to convert cholesterol into bile. However, the real lipid-lowering effect of the two drugs is not ideal. With the theoretical support, the penicillin extract mevastatin can effectively inhibit the activity of HMG, and another lovastatin, a purified fungus, 1987 entered the market and was named Mei Jiangzhi. 1992, Merck went public under the new name of simvastatin, in order to deal with the embarrassment of patent of small molecule drugs. However, pravastatin developed by 13 * * * succeeded in killing beautiful women on the beach. The author emphatically describes the difficulty and urgency of drug research by pharmaceutical companies. Facing the huge demand market and numerous commercial competitors, R&D capability, marketing promotion and policy considerations are very important. The best way to protect patients is by no means to ban patents, and improving medical security is the right way. Lipid-lowering drugs also benefit from Lipitor, and the artificial synthesis reduces the cost and the effect is obviously smaller. Nowadays, hyperlipidemia drugs have turned to macromolecular proteins and monoclonal antibodies to cope with the embarrassing situation of difficult research and development and easy replication.
Familial hyperlipidemia is also a medical problem, with few cases and little demand, but from a fair point of view, it should not be given up, and it can often inspire and solve the confusion of epidemic diseases. For example, patients with hyperlipidemia genetic diseases lack low-density lipoprotein receptors and cannot respond to low-density proteins, or low-density lipoprotein mutates, cholesterol production loses its brakes, and the liver never stops producing. Scientists found a gene named PCSK9 from this patient, and its gene mutation led to the enhancement of this gene, which led to hyperlipidemia. Compared with statins, the efficacy of PCSK9 is amazing. Antibody is a naturally occurring protein with ever-changing structure in human body. Scientists use monoclonal antibody technology and cancer cell proliferation technology to continuously produce PCSK antibodies, which solves this genetic hidden danger.
Higher organisms can extract 38 kinds of energy currency-adenosine triphosphate from glucose molecular species, and glucose is very efficient as an energy carrier. In vivo, glucose molecules are further synthesized into more stable macromolecules, such as starch and glycogen, which are stored in muscles and liver cells. Beta cells in the pancreas secrete insulin and release it into the blood, instructing muscle cells and fat cells to absorb glucose molecules in the blood and synthesize glycogen for storage, and at the same time stopping liver cells from producing glucose. However, glucagon secreted by alpha cells has the opposite effect. When eating, blood sugar soars. Insulin should not make blood sugar too high at the peak. Specifically, glucose molecules enter β cells with the help of glucoprotein, which triggers a chemical reaction and releases insulin. When the blood sugar level is too high, the insulin in the blood circulates to the whole body, telling muscles and fat cells to store energy, and liver cells stop working.
Diabetes is a disease of wealth, which can be divided into 1 type and type 2. 1 type is a kind of juvenile diabetes, and immune cells attack β cells crazily. Type 2 diabetes is a mainstream diabetes, in which muscles, fat and liver cells lose their response to insulin. Overweight, hyperlipidemia and lack of exercise are all important risk factors for type 2 diabetes. Hyperglycemia is that the body loses the storage capacity to absorb blood sugar molecules and enters the urine through blood circulation. Brain function depends almost entirely on the steady supply of glucose. When the human body is short of sugar, it will consume body fat to produce ketone bodies, and the synthesis process of ketone bodies will lead to blood acidification and ketoacidosis. The kidneys repeatedly absorb the waste in the blood and recover water as much as possible. People with glucose will drink a lot of water to urinate.
For 1 type diabetes, scientists discovered the function of insulin after slaughtering a large number of dogs, pigs and cows, and began to purify insulin from animals to treat hyperglycemia patients (the insulin of pigs is closest to humans, so it is no wonder that it is always said to be pigs), so tons of animal pancreas were sent to factories, but the cure of patients depends on the health of animals. Later, the protein structure of animal insulin was obtained by 12 insulin puzzle technology, but it did not reduce the insulin demand of animals. 1982, the first person went on the market with insulin. Tektronix has produced human insulin by recombinant DNA and bacterial technology, and even made a brand-new protein drug superior to natural insulin. However, in order to prolong the effect of drugs, pharmaceutical companies extend the half-life of insulin through genetic modification, or invent an insulin pump to communicate with blood vessels and monitor blood sugar levels in real time.
For type 2 diabetes, scientists unexpectedly found that metformin (similar to the composition of goat beans that poisoned goats) can improve human sensitivity to insulin, but its mechanism is still unknown. After the discovery of hormones, scientists discovered two kinds of protein related to insulin, GIP and GLP- 1. When glucose enters the small intestine, it stimulates the secretion of these two hormones and indirectly stimulates insulin secretion. However, gastrin has a short survival time in the body, so it cannot stay in the body for a long time by injection. Scientists can only find ways to transform GLP- 1 to make it survive in vivo for a long time, so as to obtain liraputide similar to GLP- 1, or destroy DPP-4 protease through agliptin to prevent it from destroying GLP- 1. However, the complications caused by chronic diabetes are still difficult to break through.
There are many roads worth looking forward to in the future. Scientists have tried to transplant pancreas, but taking drugs that suppress immune function requires patients to live in a closed glass box. Someone proposed an artificial pancreas. At present, some companies use embryonic stem cells to culture in Petri dishes at fixed points, put them into boxes and implant them under the skin, and organize immune cells to spy through the filter holes. Another idea is to turn excess cells in the human body into beta cells, which is a dream. It can be seen that hyperglycemia is still a big medical problem, but we still have to dream.
In addition to eating food, the author also patiently learned a lot of medical knowledge, such as discoveries in the human body, various medical research methods and medical research and development process. It can be seen that the operation of the human body is not simpler than the universe. Faced with those visible and visible complex structures, scientists have been pushing the development of medicine with great patience. Of course, they want to thank countless cows, rabbits and rats who have made sacrifices for human health. They were born with diseases, or were forced to get sick. Nature has never been fair. Finally, the author extracts the great method to eliminate the rumors in the circle of friends-to verify whether the material threat is reasonable, and to actively confirm whether it is satisfied: evidence from epidemiology (whether the material is related to health under large-scale samples), scientific research (strictly controlling conditions, whether the material can induce experimental products) and clinical medicine (large-scale clinical trials). Don't rashly say that XX is poisonous just because the aunt next door ate XX.