[aruanan]

Besides, there is very little de novo lipogenesis in the human body.

This paper argues otherwise. Do you have any more up to date references than this?

Fructose, insulin resistance, and metabolic dyslipidemia

A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG) synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism.

The paper is a 2005 review paper. The study they cite for enhanced de novo lipogenesis is a 1993 paper (Am J Clin Nutr November 1993 vol. 58 no. 5 754S-765S). Not exactly recent.

At any rate, the amount of de novo lipogenesis in humans is very small. You could significantly enhance it and still have a relatively small contribution to total body fat. And all this would still be in the context of total kilocalorie intake. If your intake does not exceed your output, it wouldn't make any difference at all if some fructose led to de novo lipogenesis. You cannot store more energy than you take in. It would only make a difference if intake exceeded output. And you'd still wind up with the same problem. Your fat increase will be to the degree that your energy intake exceeds your energy output. Regardless of where the fat comes from (dietary intake versus de novo lipogenesis--which requires energy), it will not increase your body weight unless your energy expenditure falls below your energy intake.

Think of the de novo lipogenesis as an additional step that energy intake has to go through on its way to storage. That costs energy. So, in the end, if excess energy in the form of dietary fat goes directly to fat stores while carbohydrates are preferentially oxidized or if some of those carbohydrates trigger the genesis of new fat, the total amount of energy available for fat deposition can never be more than the amount energy intake in excess of energy expenditure. One could argue that an additional energy-intensive process, fat synthesis, or an increase in this process, would, for the same amount of excess energy intake, result in decreased fat deposition due to the higher energy costs in maintaining the synthesis.

[neverdem]

The paper is a 2005 review paper. The study they cite for enhanced de novo lipogenesis is a 1993 paper (Am J Clin Nutr November 1993 vol. 58 no. 5 754S-765S). Not exactly recent.

It appears that you're refering to:

Intermediary metabolism of fructose.

Most of the metabolic effects of fructose are due to its rapid utilization by the liver and it by-passing the phosphofructokinase regulatory step in glycolysis, leading to far reaching consequences to carbohydrate and lipid metabolism. These consequences include immediate hepatic increases in pyruvate and lactate production, activation of pyruvate dehydrogenase, and a shift in balance from oxidation to esterification of nonesterified fatty acids, resulting in increased secretion of very-low-density-lipoprotein (VLDL). These effects are augmented by long-term absorption of fructose, which causes enzyme adaptations that increase lipogenesis and VLDL secretion, leading to triglyceridemia, decreased glucose tolerance, and hyperinsulinemia. Acute loading of the liver with fructose causes sequestration of inorganic phosphate in fructose-1-phosphate and diminished ATP synthesis. Consequently, the inhibition by ATP of the enzymes of adenine nucleotide degradation is removed and uric acid formation accelerates with consequent hyperuricemia. These effects are of particular significance to potentially hypertriglyceridemic or hyperuricemic individuals.

Do you have anything more recent that refutes it? I'd be happy to read it. Here a more recent citation:

Fructose induced lipogenesis: from sugar to fat to insulin resistance.

Abstract
Increasing consumption of sugars is one of the contributing factors to the obesity epidemic. Both cane sugar and high-fructose corn syrup(HFCS) contain glucose and fructose. Fructose, in contrast to glucose, is known to potently stimulate lipogenesis, but the mechanisms responsible are not yet fully known. This paper reviews several possible pathways that might be involved, such as activation of pyruvate dehydrogenase, and transcriptional activation of sterol regulatory element binding protein 1c by key regulators such as peroxisome proliferator activated receptor-γ co-activator 1β and the splice variant of X-box binding protein 1. Together, these pathways might establish a feed forward cycle that can rapidly increase hepatic lipogenesis. As a result, dietary fructose might promote the development of nonalcoholic fatty liver disease, which in and of itself, can result in hepatic insulin resistance, a key feature of type 2 diabetes mellitus.

I never heard of nonalcoholic fatty liver disease when I was in medical school two decades ago, but I can find stories about it in Family Practice News now. I used to think that a six carbon monosaccharide wouldn't have any different effects from another six carbon monosaccharide, but fructose makes me question that assumption. The HFCS used in soft drinks is 55 % fructose and 42 % glucose. Couldn't the excess fructose shift the equilibrium from oxidation to esterification of nonesterified fatty acids?

Using fructose and (nafld or nonalcoholic fatty liver disease or non-alcoholic fatty liver disease) at PubMed gets 40 citations.

[grey_whiskers]

One could argue that an additional energy-intensive process, fat synthesis, or an increase in this process, would, for the same amount of excess energy intake, result in decreased fat deposition due to the higher energy costs in maintaining the synthesis.

Hast hit it, friend wiggle.

Next couple o'questions...

1) Is it possible that the body keeps track of its amount of brown vs. white fat, exercise levels, and both TOTAL caloric intake and % of protein / carbs / fat, and then decides how much food to absorb, or to process for energy once absorbed, instead of excreting it unused? I.e. is the number of calories your body "sees" when deciding to become overweight, necessarily the number of kcal which would be released by oxidizing the food in a bomb calorimeter?

2) How well quantified are the various metabolic energy pathways? Can the body "deliberately" change to more or less efficient was of burning up your food depending on the amount of white / brown fat and your diet? Can one reset these markers over the short or long term by tweaking the *composition* of the diet rather than total calories?

Cheers!