ghrelin, growth hormone, and IGF-1

ghrelin

GH release, food intake, energy and glucose homeostasis, cell proliferation and differentiation are a function of this hormone. Further, this Yale study reveals that ghrelin has a positive influence on learning and memory processes, and cognitive enhancing effects of ghrelin have also been reported.

At the same time, ghrelin stimulates appetite and adiposity in animals as shown here, where fasting increases ghrelin, and re-feeding reduces ghrelin. This indicates that ghrelin is a leptin antagonist.

Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin discusses that GH release is a function of ghrelin and reports results that

indicate ingested medium-chain fatty acids are directly used for the acylation of ghrelin.

Significance of ghrelin acylation

This article explains that ghrelin is activated by growth hormone secretagogue receptor GHSR-1a. According to Entrez Gene, GHSR-1a is the receptor for ghrelin and defines a neuroendocrine pathway for growth hormone release.

Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities

There is an unacylated form of ghrelin, des-acyl ghrelin, which does not bind GHSR-1a and has no endocrine activity.

So it appears as though acylation of ghrelin is required for it to exert effects such as growth hormone release.


growth hormone (GH)

With this information on how MCFA relates to ghrelin relates to growth hormone, this study on MCFA effects on GH now makes more sense.

MCTs exert aging and anti-aging effects on brain

Fairly recent study which investigates the Effect of two medium chain triglycerides-supplemented diets on synaptic morphology in the cerebellar cortex of late-adult rats.

This study was to investigate the consequences of MCTs on the aging brain, and so the rats used were late-adult (old) rats.
At 10%-20% of diet content, MCTs induced senescent effects. At 20%+ MCTs, no changes were detected.

aging
In MCT-fed rats, MCTs "accelerate aging in the stratum moleculare of CA1 (SM CA1)". Recall that the stratum moleculare (SM CA1) is located in the hippocampus, the area of the brain that determines long-term memory and spatial navigation.

anti-aging
"..."antiaging" in the outer molecular layer of dentate gyrus (OML DG).."
the dentate gyrus

• contributes to neurogenesis (new neurons) and the formation of new memories.
• may have functional role in managing stress & depression
• dentate gyrus growth is associated with aerobic exercise

don't feed medium-chain triglycerides to your cat

Have a look at Aversion of the cat to dietary medium-chain triglycerides and caprylic acid;

cats rejected food with MCTs entirely at the C8 chain lengths and lost weight.

"cats would not eat after first tasting the diet"

lol

mitochondria

Research shows that both physical training and medium-chain fatty acids have positive effects on mitochondria. Dr. B G (animalpharm) has some awesome posts that have brought the importance of mitochondria to my attention; you might want to skim a few of her articles to help understand and appreciate their importance first.

• ketogenic diet appears neuroprotective...enhanced mitochondrial function...
• gene-environment interaction part II
• mitochondrial adaptation to exercise + training
  

mitochondria and medium-chain fatty acids (MCFAs)


This study was performed on rats to measure mitchondria capability to provide ATP. The rats were fed a ketogenic diet of medium-chain triglycerides. Mentions that ketone body intake improves cardiac metabolic efficiency and exerts a cardioprotective antioxidant action.

CONCLUSION: showed that MCT-ketogenic diet improves mitochondrial capability to provide ATP, and mitochondrial area (size) increased in cardiac tissue.

Enhancement of muscle mitochondrial oxidative capacity -- potent tissue-specific effects of medium-chain fatty acids

MCFAs demonstrated improved glucose tolerance and enhanced muscle mitochondrial oxidative capacity - "the increase in oxidative capacity was substantially greater in MCFA-fed animals" (50-140% vs 20-50% for LCFAs)


mitochondria and training

This article brings up

• "Endurance training induces a multitude of adaptations that result in increased fat oxidation"
• "duration and intensity of exercise training required to induce changes in fat oxidation is currently unknown"
• "Ingestion of carbohydrate in the hours before or on commencement of exercise reduces the rate of fat oxidation significantly compared with fasted conditions"
• "fasting longer than 6 h optimizes fat oxidation"
• "at oxidation rates have been shown to decrease after ingestion of high-fat diets, partly as a result of decreased glycogen stores and partly because of adaptations at the muscle level."

Low-fat diet alters intramuscular substrates and reduces lipolysis and fat oxidation during exercise.

High-fat diet elevates resting intramuscular triglyceride concentration and whole body lipolysis during exercise.

UCP2
UCP2 is a mitochondrial protein.
UCP2 appears to be used in areas of the brain for the purpose of modulating energy balance.
overexpression of UCP2 has been reported to be neuroprotective against oxidative stress in vivo and in vitro

greater effects of MCFA associated with lower body weight

Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue.

All subjects in the study were overweight men. Diets were MCT oil vs olive oil. Lower body weight was associated with greater both energy expenditure, fat oxidation, and fat loss with MCFA.
CONCLUSION:
"These data suggest that shunting of dietary fat towards oxidation results in diminished fat storage, as reflected by the loss of BW and subcutaneous adipose tissue. Furthermore, MCT consumption may stimulate EE and fat oxidation to a lower extent in men of greater BW compared to men of lower BW, indicative of the lower responsiveness to a rapidly oxidized fat by overweight men."

very low calorie dieting with MCTs

Value of VLCD supplementation with medium chain triglycerides.

 4-week study done on obese women. Three diet groups, keeping in mind they were all low-calorie: low-fat, LCT (long chain triglycerides), or MCT (medium chain triglycerides). MCT group showed significantly more weight loss, where more of the weight loss was from fat loss than the other. The MCT group showed more ketones, not very surprising if you've seen other studies on MCTs, this is the norm. Satiety was higher with MCTs. MCTs vs LCTs here showed MCTs in diet lead to greater fat loss and more protein (muscle) sparing.


Researchers noted that these effects declined over time suggesting "metabolic adaptation". From personal experience I can confirm this.

MCTs vs LCTs

Endogenous fat oxidation during medium chain versus long chain triglyceride

compares a MCT blend with butter vs beef tallow. so this study is comparing sat. fat vs sat. fat. Why butter + MCT instead of just MCTs? Nearly no one wants to eat MCTs straight. This study is dealing with human subjects here.

"With the MCT diet, but not the LCT diet, combined cumulative fractional LCSFA oxidation (P < 0.03), net LCSFA oxidation (P < 0.03), and percentage dietary LCSFA contribution to total fat oxidation (P < 0.02) were increased"
"CONCLUSION: The capacity of MCT to increase endogenous oxidation of LCSFA suggests a role for MCT in body weight control over the long term."

Here's a study that looks at weight recovery after low food intake (i.e. after a "diet"). Shows that lard results in more body fat regain than coconut oil (MCTs).

Another PubMed citation involving non-insulin-dependent diabetes mellitus (NIDDM) subjects in a short-term study which compared the effect of substituting long-chain triglycerides with medium-chain triglycerides. The MCT group showed greated fasting concentrations of ketone bodies.
The following from the abstract doesn't mean much to me, but may for others:
"MCT-containing diets increased insulin-mediated glucose metabolism in both diabetic patients and nondiabetic subjects. In diabetic subjects, this effect appears to be mediated by increases in insulin-mediated glucose disposal."