Nutrient Fates after Absorption

Nutrient effects: post-absorptive interactions BY ERIC JEQUIER   (1995)

After a meal, the metabolic fuel selection at the whole-body level depends on the plasma concentrations of nutrients such as glucose, non-esterified fatty acids (NEFA) , amino acids, and on hormonal responses. Over the last 10 years, there has been great interest in studying the metabolic effects following the ingestion or the intravenous (i.v.) infusion of the three macronutrients, carbohydrate (CHO), fat, and protein (or amino acids for i.v. infusion). The aim of the present brief review  {I'm thinking it's not so brief!}  is to summarize the main mechanisms which determine the post-absorptive interactions between the nutrients.

This is an older paper, but still recent enough to provide some good info on the basics.  I'm going to do something a bit different with this one and I otherwise would be quoting huge chunks.  So I'll do bullet point summaries with select summary quotes from the paper in italics.

Carbohydrates:

• Four fates:  Oxidation, Storage as Glycogen, Triglyceride synthesis (TAG, de novo lipogenesis) or conversion to gluconeogenetic precursors.

"It is to be emphasized that other metabolic pathways for disposal of dietary CHO, such as conversion into TAG or into non-essential amino acids, are not quantitatively important."

• Our extracellular capacity for glucose (e.g. circulating) is only about 10g so most dietary glucose that cannot be immediately oxidized is converted to glycogen to store for future use.  
• Upon ingestion of 100g glucose, about 40g is oxidized, 50g stored as glycogen and 10g not yet absorbed in 3 hours.  Fuel partitioning for energy in that period is 60% from glucose, 25% lipid oxidation and 15% protein oxidation.
• Normal glycogen stores are between 250 - 500g, on the order of magnitude of "normal" carb consumption of 250-300g/day 
• Several studies are listed indicating that excessive carbohydrate ingestion is accommodated for by increasing carbohydrate oxidation and glycogen synthesis.  Minor lipids formed by DNL were subsequently oxidized.  

"The important point is that there was no gain of fat by de novo lipogenesis, as a small amount of net lipid oxidation was observed."

• Chronic overeating of carbs results in an increase of glycogen stores by about 500g before DNL becomes significant.  Only with chronic overfeeding and saturated glycogen stores does conversion of carbs to fat become significant.

"de novo lipogenesis is not an important pathway in humans"

Carbohydrates do not contribute to "fat accumulation" by excess carbs being converted to fat.

Dietary Fats

• This consolidated section generally confirms my understanding of adipose tissue as a transient regulator of NEFA levels.  
• Most dietary fat transported in chylomicrons is taken up by fat tissue.  Insulin does suppress NEFA release, but never entirely.

"It is to be emphasized that adipose tissue LPL activity does not necessarily imply net storage of lipid; from 180 to 300 min after a meal adipose tissue is able to convert circulating TAG into NEFA, not storing the majority of the fatty acids derived from circulating TAG. Human adipose tissue is not simply a reservoir for food energy, but it is an important tissue for the disposal of circulating TAG postprandially."

• Dietary fat does not induce marked increases in lipid oxidation rates in an acute manner.  I previously blogged on increased dietary fat increasing lipid oxidation after several days .

"It can be concluded that within a reasonable range of CHO-energy : fat energy, the addition of fat to a meal does not substantially increase fat oxidation."

Glucose / Fatty Acid Competition

• There is evidence of competition between glucose and FA's as oxidative substrates, the exact mechanism is not known but the Randle hypothesis is not applicable to humans.
• Increases in NEFA correlate with reductions in insulin-mediated glucose oxidation
• Elevated NEFA plays a role in the development of insulin resistance

Interactions of the Three Macronutrients ~ I.V. Infusion Experiments

Amino Acids:

• AA's increase gluconeogenesis rate and glucose production in the liver along with a slight rise in glucose oxidation.
• AA's stimulate insulin and therefore increase glucose clearance. 
• AA's do not inhibit glucose oxidation in contrast to FA's

Fatty Acids:

• Lipid infusions do not stimulate glucose production in the liver but do increase gluconeogenesis.  I find this confusing because I assume GNG produces ... well ... glucose.  Or perhaps glycerogenesis takes the glucose --> glycogen?
• NEFA/FFA infusions are to be interpreted with caution anyway with regard to dietary nutrients.  Circulating dietary fats are mostly as chylomicrons.

FA's + AA's:

• Simultaneous infusion led to increased gluconeogenesis and peripheral insulin resistance, but this is offset by insulin release when fed to normal individuals.

Post-absorptive Protein:

• Nitrogen balance is fairly tightly controlled
• Ingested protein stimulates protein synthesis and turnover
• Increased energy expenditure (TEF of protein) is accounted for by the metabolic "cost" of protein synthesis.

Ethanol Surprise!:

• Ethanol in a meal suppresses lipid oxidation (no surprise there)
• Ethanol has about a 20% TEF!!  

"N balance is achieved on high or low (but sufficient to meet requirements) protein intakes; similarly, CHO balance is also precisely regulated since the glycogen stores are stable from day-to-day, and de novo lipogenesis from CHO is not an important pathway in humans. Thus, both protein and CHO intakes promote their own oxidation, and the 24 h intake of these nutrients determines the respective amounts oxidized. By contrast, fat intake does not promote its own oxidation, and fat balance is not regulated by oxidative metabolism. Fat balance mainly reflects changes in energy balance. The regulation of fat balance is, therefore, much less precise than those of protein and CHO.  This is to be expected because large daily errors in fat balance involve amounts which are very small in comparison with the body’s fat reserves (Flatt, 1987). In addition, errors in fat balance do not elicit appropriate responses in food (and fat) intakes that could ensure the maintenance of fat reserves (Blundell et al. 1993)."

This article goes a long way to explain why the "Standard American Diet" or "Western Diet" is fattening.  Metabolic signalling is tightly controlled for carbs and proteins, but if one eats 100g fat or 200g fat in the context of their diet it's not "sensed" metabolically in the postprandial sense.