Diet, Carbs, Fat and Weight Loss

Glucose and Insulin Are Required to Gain or Retain Body Fat

The essential fact of weight gain or loss is that fat (triglycerides, TGs) stored in fat cells (adipocytes) is made from glycerol (from glucose) and fatty acids (from the blood or recycled from previously stored fat droplets.) Adipocytes must import glucose to make glycerol and TGs.

Glucose Is a Carbohydrate

Glucose is a sugar or carbohydrate. Once again the word tells the story, i.e. carbohydrates consist of carbons that each have a hydrogen, -H, and a hydroxyl -OH attached. Since each glucose has six carbons, then it can be roughly approximated as (H-C-OH)6. This is convenient notation, because this lets glycerol be considered as a three carbon sugar, i.e. (H-C-OH)3.

Glycolysis Can Convert Glucose into Two Glycerols

The central metabolism of all cells is called glycolysis, literally breaking glucose. The products of glycolysis are usually high energy electrons (carried by NADH), two pyruvates and ATP (chemical energy). Active cells with access to oxygen can use their mitochondria to accept the high energy electrons and pyruvate, and generate lots of ATP and CO2. Fat cells can bring in glucose by glucose transporters, make glycerol instead of some of the pyruvate and use the rest of the pyruvate by mitochondria to make fatty acids (instead of ATP.)

Fats Have Three Fatty Acids Attached to Glycerol: Triglycerides

Fats, triglycerides, are made in a series of biochemical reactions catalyzed by enzymes. The enzymes first make glycerol phosphate from glycerol and NADH, from glycolysis. Then the fatty acids are attached. The fatty acids can come from three sources: from glycolytic pyruvate, from fatty acids offloaded from the blood stream and from constantly recycled stored fat. Regardless of the source of fatty acid, new glycerol phosphate is needed for TG production in fat cells

Insulin Is Required for Glucose to Enter Adipocytes

Glucose is transported into adipocytes by specialized proteins embedded in their cytoplasmic membranes. A few glucose transporters are always present to supply enough materials and energy for basic maintenance of the adipocytes. Even with very high blood sugar (glucose), the glucose uptake of the adipocytes will not be increased without an increase in the number of glucose transporters in the cytoplasmic membrane. Insulin released into the blood by the pancreas in response to an increase in blood sugar, stimulates the adipocytes to introduce more glucose transporters into their membranes and glucose is actively transported into the adipocytes. The adipocytes then convert the glucose into glycerol, fatty acids and ultimately stored fat.

Without High Blood Sugar and Insulin, Adipocytes Lose Fat

Fatty acids in adipocytes are constantly be converted to fats and then released from storage as they are enzymatically removed from the fats to reappear as free fatty acids. As a consequence, the absence of extra glucose in the adipocytes will mean a shortage of glycerol and a net accumulation of free fatty acids from stored fats. Excess fatty acids will mean that fatty acids will be removed from rather than deposited in adipocytes.

Weight Gain Occurs with High Blood Sugar Regardless of Fats Eaten

Fat will be produced in adipocytes if there is high blood sugar and insulin production, because the fat already stored in the adipocytes will be recycled into fat, any fat in the diet will be converted into stored fat and glucose transported into adipocytes will be converted into fat. In addition, protein in the diet and potentially in muscle, will also be converted into stored fat.

Weight Loss Occurs with Low Carbohydrate Diets Regardless of Fats Eaten

Fats that are eaten without sufficient carbohydrates to cause a rise in blood insulin, are metabolized for energy in liver and muscle. Excess fat ends up being secreted into the gut by the gall bladder and lost as feces. Type I diabetics without insulin cannot get enough glucose into their cells to make fat and cannot gain weight without insulin. The amount of glucose, as simple carbohydrates (sugar or starch), needed to raise blood sugar to trigger a rise in insulin production is typically 30 to 50 grams per meal. Hunger, a response to a drop in blood sugar, prior to the next meal is a typical indication of insulin production and fat storage.

Diet, Nutrition and Health

These are my generalizations (some would say prejudices) from 40 years of experience in plant biochemistry and molecular biology:

Plant Secondary Compounds Are Defensive and Toxic

The development of plant secondary compounds (all of the compounds that are not part of metabolism or structures) is in response to pathogens, herbivores and pollinator/disseminator attractants -- development of these compounds has nothing to do with humans. Examples: Nicotine and caffeine are very toxic to herbivores and are present in plants for protection. Humans learn to play with toxic plant chemicals, just as they have learned to play with fire and explosives.

Plants Are Not There For Us

People have learned to exploit local plants for protection against local human pathogens, but there is no selective advantage to plants (except for domesticated plants) for useful plants to grow near humans. This logic would suggest that rats and mosquitoes, that flourish near human habitations, are there because of their human utility. Human live near places were useful plants grow.

Grains Are Unhealthy

One of the biggest problems with food processing is separating the inflammatory parts = starch and omega-6 oils, from the nutritive parts, the so-called anti-oxidants, vitamins, proteins, etc. Grains, even so-called whole grains, are simply too enriched for starch and inflammatory oils to be healthy. They are not safe to eat in large amounts. Leafy plant parts are healthy, but even those parts are not good in large amounts from a single plant species. Humans are browsers, because the plant secondary compounds are uniformly toxic, but can be tolerated better in a mixture of different toxicities.

Starch Is Inflammatory

Starchy foods should be treated like a fish. The starch should be pared away and discarded, like the fish gut and bones. (The guts and bones could actually be processed to make them nutritious. Not so with the starch. The starch should be fermented.) The potato skin should be eaten and the rest discarded, just as an aphid secretes as honey dew the extra sugar it sucks in from a plant leaf.

Cereals Are Inflammatory

Breakfast cereals are a dietary abomination. They contribute immensely to obesity, inflammation and chronic disease. Oatmeal for cardiovascular health is a total fraud. The fiber might be useful, but the high starch causes cardiovascular disease. Grains/cereal are the foundation of the chronic disease pyramid.

Fructose is Toxic

Fruit juices are another fraud. The juice (fructose) should be removed and discarded. The fructose is very unhealthy. Mice are given type II diabetes for research purposes by feeding them fructose (especially high fructose corn syrup.) Fructose is avoided in the beef industry, because it causes rapid cross-linking of collagen and leads to tough meat. The same thing happens in humans who eat fructose, it causes aging of the skin and other tissues. High fructose corn syrup is a commercial addiction -- it is hugely profitable as a sweetener -- and that is why it is still used, even though it is grossly unhealthy. It will eventually be removed from the market after the industry is protected from subsequent law suits. It is equivalent to the tobacco industry -- too lucrative to eliminate.

Phytic Acid

The active ingredient in fiber that provides its benefits is phytic acid, the same chemical that people are trying to eliminate. Phytic acid acts as a chelator. I don't think it is actually a problem. The problem comes from extracting cations from the phytic acid before it is eaten. Phytic acid should go in saturated, so that it doesn't contribute to deficiencies. The actual problem is that the diet is already low in minerals, because of eating processed foods that are mineral deficient.

Enzymatic Detoxification: P450, Glycosylation and Secretion

Humans are adapted to plant secondary metabolites by the abiltiy to enzymatically detoxify [using p450 and glycosylating (adding glucuronic acid)] and secrete the toxic compounds. These chemical modifications that occur in the intestines and liver are usually effect. They also work on drugs and that is how we eventually clear these compounds from our systems. Grapefruit and black pepper inactivate these enzymes and alter the way we metabolize plant toxins and drugs. The detox enzymes can also convert innocuous compounds into toxins and carcinogens. That conversion is the basis for using liver enzymes in the Ames Test for carcinogens. The activity of the enzymes is dependent on recent diet, so it would make sense to gradually change the amount and type of vegetables that are eaten in a meal to permit the detox system to adjust.

Glucose and Insulin Cause Fat Accumulation

Fat accumulation is dependent on dietary carbohydrates and insulin. Fat and serum lipids accumulates with a high carbohydrate diet and decrease on a low carbohydrate diet. This is more important than the number of calories consumed.

Inflammation Not Serum Lipids Cause CVD: Statin Are Unnecessary

Inflammation is the source of chronic degenerative diseases. Serum lipids are only secondary factors. Statins lower serum lipids, but do not impact cardiovascular health unless they also lower inflammation. Lowering inflammation lowers serum lipids and decreases cardiovascular disease. Statins appear to be a very expensive way of treating cardiovascular disease dependent on their side effect on inflammation. Modest dietary and lifestyle changes are much more effective, cheap and safe than statins.

Leptin and Diabetes

Fat cells produce the hormone leptin. Early experiments showed that leptin could ameliorate some of the effects of mouse models of type I diabetes, but it was always thought that the leptin just improved the activity of the small residual amounts of insulin produced by the rats. A recent experiment with genetically insulin deficient NOD mice, shows that leptin expressed by a virus infection reverses the symptoms of diabetes.

The NOD mouse strain is defective in the hormone, IL-2, that preserves tolerance to self proteins. As a result, a high percentage of the NOD mice develop symptoms of type I diabetes melitis, high blood glucose and ketosis. These animals will die without injected insulin.

In recent experiments, the NOD mice showing symptoms of diabetes were injected with a strain of adenovirus that had been engineered to express leptin. The leptin-expressing NOD mice displayed a rapid reversal of diabetes symptoms and began to gain weight normally. The high blood sugar and ketosis in NOD mice was stimulated by glucagon release in response to lack of insulin. Leptin stopped the glucagon release and reduced additional production of glucose by the liver and lipid oxidation that yielded the ketosis.

Muscle access to glucose in the NOD mice was restored by leptin by the induction of insulin-like growth factor 1 and its receptor. The NOD + leptin mice had normal blood sugar, but ate half the normal amount and had no body fat.

These are very promising results for type I diabetics, because it indicates that insulin injections are not the only approach to treatment. Stimulation of leptin production may be very useful and this new approach is being intensely investigated.

reference:
Yu X, Park BH, Wang MY, Wang ZV, Unger RH. 2008. Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci U S A. 105(37):14070-5.