Stored fat
may come from diet or de novo lipogenesis (DNL). De novo lipogenesis refers to the conversion of dietary carbohydrate (CHO)
into fat.
The physiological functions of de novo
lipogenesis are (1):
1. There are no functions (vestigial pathways in humans);
2. Necessary in embryonic development – for central
nervous system lipid synthesis (vestigial
pathway in the post-natal life);
3. Important on low-fat diets – suppressed by
un-natural modern diet (vestigial pathways culturally);
4. Only important after long-term surplus carbohydrate
(glycogen overflow pathway);
5. Serves signal or regulatory functions (eg.
antiketogenesis, tissue fat oxidation, insulin synthesis, etc).
The regulation of acetyl-CoA carboxylase, fatty acyl synthetase, malonyl-CoA and other components of the enzymatic pathway is well known (1,2,3), however the quantitative importance of DNL has remained an area of uncertainty until recently (1).
Net lipogenesis is quantitatively small in humans subjects following a typical diet (4,5,6,7,8). Net lipogenesis measurements using respiratory gas exchange (4,5) or from stable isotope tracer studies (4,5) indicate that under normal conditions the rates of lipogenesis from carbohydrates are small.
Indirect estimates have suggested a small quantitative contribution from DNL in humans (6,9,10,11,12). Direct measurement of hepatic DNL by isolation of plasma very low density lipoprotein (VLDL)-TG, which are secreted from the liver, reveals that hepatic DNL makes a quantitatively minor contribution to secreted VLDL-TG under most dietary conditions in humans (10,11,12).
Others show that hepatic lipogenesis is absent or very small in healthy subjects (7,8,12). Another study with 68% of complex carbs resulted in minimum hepatic lipogenesis (13). More studies confirmed the absence of a significant flux through hepatic lipogenesis under carbohydrate overfeeding conditions (9,14).
Adipose tissue lipogenesis in both lean and obese subjects is equally small as hepatic lipogenesis (2-5g/d) under free living conditions (15).
The use of long-term 2H2O administration to human subjects allows measurement of
the dynamics of adipose tissue components, showing that turnover of all
elements is slow, and DNL contributes ∼20% of new triglycerides in adipose tissue (16).
When a single high-carbohydrate meal is consumed, dietary carbohydrate merely has the effect of reducing the rate of fat oxidation, showing that the conversion of carbohydrate to fat is not an important pathway for the retention of dietary energy and for the accumulation of body fat (17).
Even with massive carbohydrate overfeeding (1000kcal) for 21 days there was only a conversion of 332g of glucose to fat from a total of 5250g (250g x 21 days), or only 6% (18). In another study with a mean energy surplus of 4.1 MJ/d (~1000kcal), carbohydrate oxidation predominated, but the RQ did not exceed 1 during any 24-h period, suggesting that despite this large energy surplus, there was no net lipogenesis (19).
In an overfeeding study of 14 days (20) even though de novo lipogenesis in tissues such as the liver could not be definitively determined, the calorimetry data indicated that net lipogenesis from carbohydrate did not occur.
This is no different in obese subjects with either glucose of sucrose overfeeding (50%), De novo lipogenesis increases to the same extent in lean and obese women but does not contribute greatly to total fat balance (21).
And if you are thinking of fructose, here is what happens to fructose, again based on isotopic tracer studies in humans, only a small percentage of 50-150g of ingested fructose (<1%) appears to be directly converted to plasma TG (32):
Special conditions
lead to an increase in hepatic lipogenesis, even in eucaloric conditions, such
as in a diet with 10% or less energy from fat and 75% energy from carbohydrates
(8,22).
This contrasts with minimum lipogenesis in a diet comprised of 40% fat and 45% carbohydrates (8). Another condition is when more than half of carbohydrates are consumed as simple sugars coupled with only 10% of fat (23).
This contrasts with minimum lipogenesis in a diet comprised of 40% fat and 45% carbohydrates (8). Another condition is when more than half of carbohydrates are consumed as simple sugars coupled with only 10% of fat (23).
Perhaps the greatest increase
recorded was in a 7 day progressive carbohydrate overfeeding study in which,
after glycogen depletion by diet and exercise, 3 subjects received a diet extremely
low in fat (3%) and 86% of carbohydrate (24). After glycogen stores were
saturated, massive intakes of carbohydrate were disposed of by high
carbohydrate-oxidation rates and substantial de novo lipid synthesis (150 g
lipid/d using 475 g CHO/d) (24).
But overall, the total
increase rates are still small, lipogenesis is quantitatively small in humans,
and the road less travelled (25).
DNL is not the pathway of first resort for added
dietary CHO in humans.
A `functional block' therefore exists between CHO and fat in humans, analogous to the absolute biochemical block in the direction from fat to carbohydrate in all animals (1). CHO and fat must be considered separately and are probably regulated independently, by separate signals and toward separate ends (1).
A `functional block' therefore exists between CHO and fat in humans, analogous to the absolute biochemical block in the direction from fat to carbohydrate in all animals (1). CHO and fat must be considered separately and are probably regulated independently, by separate signals and toward separate ends (1).
What happens when
surplus CHO is consumed (1):
(1) CHO not converted
to fat (mysterious block);
(2) Instead: CHO burnt,
fat not; CHO stores fill up;
(3) Provides a system
for matching fuel selection to recent CHO intake (and perhaps controlling
intake);
(4) System wouldn't
work if a safety-valve (CHO to fat) were open.
Regarding point 2 "CHO burnt; CHO stores fill up; less fat is
burnt;", this happens in a caloric excess, so don't say or interpret this
as if carbs in any circumstance cannot allow fat to be oxidized. Even in a
caloric excess fat oxidation is not 100% inhibited, in fact we are burning a
mix of fuels 24h (35).
In a caloric deficit and with 45% carbs (down from 50% in the overfeeding period), following the dynamics of fuel selection (because carbohydrate oxidation is no longer a priority) the body changes fuel use to stored fat (open bar) as indicated here (31):
In a caloric deficit and with 45% carbs (down from 50% in the overfeeding period), following the dynamics of fuel selection (because carbohydrate oxidation is no longer a priority) the body changes fuel use to stored fat (open bar) as indicated here (31):
Briefly, a related question:
Often there isn´t significant differences
in fat gain (I am not talking weight/water gain) in isocaloric hipercaloric
diets with matched protein, regardless of macronutrient exchange (carbs vs.
fat) in excess (33). In some cases it can be less for excess carbs (20).
If DNL is practically
irrelevant even with massive carbohydrate overfeeding, how do we gain fat with
excess total calories coming from carbs?! In other words, if excess carbs are
stored as glycogen, oxidized and not converted to fat in a significant way,
from where comes the fat gained? Precisely
from the dietary fat in the same diet! Because carbs decrease fat oxidation as they assume priority in fuel selection,
coupled with the fact that fat does not stimulate it’s own oxidation (26-30) and is more
efficiently digested and stored than carbs; in other words body fat still comes
from dietary fat.
Remember, when you ingest more carbs you decrease lipolysis and
fat oxidation but at the same time you
are eating less fat and storing less fat; conversely if you are eating less carbs you oxidize more fat but at the same time you are also eating
and storing more fat.
Fat balance = intake - oxidation
Methodology
Indirect methods
Back in 1960s, Hirsch et al conducted indirect estimates of the turnover rate
of adipose tissue fatty acids (FA) in humans (10). At the time methods such as silicic acid
chromatography with columns and thin layers and also gas-liquid chromatography
(GLC) were already developed for the study of complex lipid mixtures.
Using gas-liquid
chromatography (GLC) and sample randomization, it was concluded that adipose tissue FA composition generally reflects
the FA composition of diet, and that it may take up to 6 months for adipose
tissue FA composition to change in response to a change in dietary FA
composition, which may imply that the residence time of adipose tissue
triglyceride (TG) is ∼6 months (10).
The triglyceride makes up 99% of the adipose lipid. De novo lipogenesis (DNL)
was estimated to make a minor contribution to stored fat.
Another useful indirect method for the replacement
rate of adipose tissue lipids is the rate
of appearance (Ra) of plasma glycerol. Glycerol is the backbone
of the triglyceride. Lipolysis refers to the breakdown of the triglyceride into
fatty acids and glycerol; the triglyceride stored in adipose tissue is hydrolyzed by
a hormone-sensitive lipase to produce free fatty acids and glycerol (1).
Whole body lipolysis, based on Ra glycerol,
is ∼1 mg·kg-1·min-1
(7,26), or ∼100 g fat/day in a nonobese 70-kg subject compared with adipose tissue
mass of ∼15 kg, or about 0.6%/day of total adipose triglyceride
tissue with a residence time of ∼170 days
(6months) (16).
Direct methods
Direct
methods for the analysis of adipose tissue dynamics requires metabolic labeling for direct
measurement. However, the labeled
precursor must last for a long enough time to achieve detectable
incorporation into adipose-triglyceride, due to the large pool size and slow
turnover of adipose TG.
Another
issue is that glycerol is not utilized
effectively by adipocytes (27), and glucose (one precursor for the α-glycerol phosphate in adipocytes, the other being
pyruvate) is an inefficient label and not practical for long-term labeling
studies. Furthermore, different FA may
have different turnover rates in adipose-TG.
Another method
for measuring the synthesis of TG in adipose tissue is using heavy water
(deuterium oxide (2H2O)) based on the
incorporation of 2H from 2H2O in the glycerol
moiety of TGs (28,29). This is followed by mass spectrometric analysis and
application of mass isotopomer distribution analysis (MIDA) (30). This
technique is very practical and easy to perform for long-term labeling studies,
at least in animals, by simply drinking 2H2O-enriched
water.
Conclusion
Despite the somewhat popular belief that carbohydrates
get stored as fat, specially sugars, de novo lipogenesis is quantitatively small in humans, carbohydrates
only have the effect of suppressing fat oxidation post-prandially (after a meal) and clearing some
fatty acids from the blood via insulin secretion, and so does protein by the
way (see fuel selection). Another
perspective to keep in mind is that you are not in a post-prandial state 24/7,
so don’t take this out of context as many do.
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