Extra: Glycogen, de novo lipogenesis and carbohydrates

This is an unusual post as I dont like discussing about weight loss or dietary carbs vs. fat superiority in terms of dieting. 

The metabolic advantage is a never ending discussion in the blogosphere. Recently, a more "scientific" debate has started on Peter's blog. While some prefer to argue using scientific references and basic biochemistry concepts, others use their own experience mixed with their opinions. This happens in both who defend insulin's central role in weight loss/gain and in those who state that its calories in-calories out all the way. This last group of people, when trying to dismiss the carbohydrate drives insulin drives fat storage hypothesis, use an old study as their bible. It is not surprising that the one who "popularized" this study was Carb Sane, with her famous post Nutrient fates after absorption. I wrote a quick answer some months ago, which was posted but strangely has disappeared. 

The study which basically dismisses the carbohydrate-insulin obesity hypothesis is one by Eric Jequier, called "Nutrient effects: post-absorptive interactions". I will only focus on the "Metabolic Fate of Dietary Carbohydrate" part. 

The author states:

"Although  the  glycogen  stores  are  normally maintained  within  a  relatively  narrow  range, the capacity for storing large amounts of  dietary CHO by conversion to glycogen is relatively large (Acheson et al. 1982, 1984, 1985, 1988). Fig. 1 shows that a large load of CHO (500 g dextrin-maltose  given as three meals over 5 h) to healthy subjects induces a marked stimulation of CHO oxidation over the 14 h after the first meal (240 g oxidized,  260 g stored; Acheson et al. 1985). Net lipogenesis occurred at a low rate from 5 to 10 h  after  the  first  meal, but  this lipid accumulation was  offset  by  a greater rate  of  lipid  oxidation over the next 4 h. The fat balance calculated over 14 h was negative, indicating  that the large load of  CHO did not induce a gain in  fat."

Lets review the studies used to support his statements. 

1. Glycogen synthesis versus lipogenesis after a 500 gram carbohydrate meal in man

Subjects participating in the study were 6 healthy male volunteers. They tested the metabolic effect of consuming 480g of carbohydrates from bread, jam and fruit juice, with little butter added. The results were as expected, no net lipogenesis occured, just an increase in muscle glycogen capacity. Ok, one big high carbohydrate/low fat meal in healthy subjects does not induce fat gain in the short term (10h), rather increases energy expenditure, glucose storage and oxidation. Nothing new.

2. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man.
Lets look at the subjects and methods used in the study:

"Three healthy young men, one of whom was a competition swimmer at university level, (21-22 y, 62-72 kg, 174-180 cm, and 11-14% body fat) with no family history of diabetes or obesity and who were not taking any medication, participated in this study."

Ok, we are talking about healthy, young and lean men. Is everyone healthy, young and lean?  I think most of the regular blog readers are people with weight/metabolic issues. The subjects included a competitive swimmer, a fact that in my opinion is very relevant, besides the fact that all of the subjects were lean. This somehow escapes from the people referencing this study. 

"The experiment lasted 14 consecutive days. During the first 3 d the subjects consumed a restricted diet, high in fat and low in carbohydrate, and followed an exercise program. Halfway through this period the subjects were admitted into a respiration chamber in which respiratory exchange measurements were to be continued for 10 d. After 36 h in the chamber the diet was changed to a high-carbohydrate, low-fat diet that was ingested for the following 7 d. During the last 2 d while still in the chamber, the subjects received limited amounts of a high protein diet (protein-sparing modified-fast [PSMF], ‘ı2.5 MJ or 600 kcal) essentially devoid of carbohydrate. The subjects then left the respiration chamber but continued to consume the high-fat, low-carbohydrate diet in restricted amounts for a further 2 d."

I wonder, if a massive carbohydrate intake does not promotes fat storage as the previous study suggested, why using a glycogen depleting protocol before an extended massive carbohydrate intake? Hmm...

In short, the protocol lasted 14 days in which:

3 first days: HFLC + exercise.

7 days: HCLF

2 days: PSMF (LF, LC)

2 last days: HFLC, restricted amounts.

So we have a scenario in which glycogen is depleted by diet plus exercise and then there is a massive high carbohydrate low fat refeed for seven days. Glycogen storage increases until the 4th day, in which glycogen stores had become saturated and de novo lipogenesis starts to increase. This shows that you need 4 days of overfeeding carbohydrates to start getting fat? No. This shows that in LEAN HEALTHY YOUNG SUBJECTS, AFTER A GLYCOGEN DEPLETING PROTOCOL, a relatively well known phenomenon called GLYCOGEN SUPERCOMPENSATION occurs. 

I dont think we can extrapolate these results to everyone nor this study shows that you can eat 500g everyday and not get fat. Specially if you are not lean and/or healthy.

3. Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal.

I find odd the use of this study to support the author's hypothesis. Subjects consumed either a high fat, mixed or high carbohydrate diet during 3-6 days preceeding the test. From the abstract (unfortunately I dont have access to the full-text):

"CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet."

This study shows what is an already known fact about high fat diets and carbohydrate loading. HFLC reduce glucose oxidation and increase non-oxidative glucose disposal, ie. glycogen stores. Although net lipogenesis was small (9g on the high carbohydrate diet), measurements were done for 24 hours. While not significant for body composition in the short term, the metabolic effect might be significant, specially considering the effect a high carbohydrate meal has on gene expression (1, 2)*. This study shows the difference between eating a 500g carbohydrate meal after a HFLC and a LFHC diet. 

4. Contribution of 500 g naturally labeled 13C dextrin maltose to total carbohydrate utilization and the effect of the antecedent diet, in man

This study is a follow up on the previous study. Nothing new to add, really. From the study:

"After the load, carbohydrate oxidation increased in each group with a corresponding decrease in fat oxidation. However, in the high carbohydrate (Fig 3C) and mixed (Fig 3B) groups, fat oxidation decreased to zero at 2.5 h and 4 h respectively after which energy expenditure was principally due to carbohydrate oxidation and de novo lipogenesis for a further 9 h and 6.5 h respectively. The negative values of lipid oxidation represent an equivalent amount of carbohydrate energy converted into lipid, ie net de novo lipogenesis. During the evening fat oxidation increased progressively and became the major energy source throughout the night in each group."

The authors concluded:

"The results imply that the more the composition of the everyday diet is rich in carbohydrate, the more full the glycogen stores become, but at the same time more carbohydrate is oxidized to provide energy. When both storage and oxidation become saturated, de novo lipogenesis can occur but not at a rate sufficient to prevent increasing blood glucose and insulin concentrations."

Summing up

It is noteworthy to mention that the author of the review, Eric Jequier participated in all of the studies shown above. The conclusion he gets from his review is the following:

"The  practical consequence  which  results from  the  different fates  of  the  ingested 

nutrients  is  that  body-weight  regulation primarily  depends on fat intake. A chronic 

excess of  fat in the everyday diet is stored and contributes to increase the adipose tissue 

mass. (...) The fat content of the habitual diet could influence the steady-state of weight maintenance. When a high dietary fat intake is chronically ingested, body-weight gain occurs."

Talk about bias. Although he mentions that "The practical implication of these findings is  that the proportion of fat and CHO energy plays an important role in body-weight regulation" he goes on saying that "The ad  lib. consumption of high-CHO-low-fat  diets induces a slow rate of  weight loss, with a spontaneous decrease in energy intake" and "Prevention of obesity should benefit from this recent advance in our knowledge of the post-absorptive effects of nutrients".

I did a quick search on more studies done by Jequier and I found these gems:

Low fat diets are preferred

Is fat intake a risk factor for fat gain in children

Failure of dietary fat intake to promote fat oxidation: a factor favoring the development of obesity

Pathways to obesity

I encourage you to check the references used in the section "Metabolic Fate of Dietary Fat". 

Studies can show whatever the author wants to. The only way of knowing and interpreting the real data is reading the data source for yourself. Or reading trustful blogs. But hey, after all, fat is what makes us ugly, fat and ultimately kills us, doesnt it?

* Some further reading on ChREBP is recommended.

Jéquier E (1995). Nutrient effects: post-absorptive interactions. The Proceedings of the Nutrition Society, 54 (1), 253-65 PMID: 7568258