Early responses of insulin signaling to high-carbohydrate and high-fat overfeeding

Abstract
Background
Early molecular changes of nutritionally-induced insulin resistance are still enigmatic. It is also unclear if acute overnutrition alone can alter insulin signaling in humans or if the macronutrient composition of the diet can modulate such effects.

Methods
To investigate the molecular correlates of metabolic adaptation to either high-carbohydrate (HC) or high-fat (HF) overfeeding, we conducted overfeeding studies in 21 healthy lean (BMI < 25) individuals (10 women, 11 men), age 20-45, with normal glucose metabolism and no family history of diabetes. Subjects were studied first following a 5-day eucaloric (EC) diet (30% fat, 50% CHO, 20% protein) and then in a counter balanced manner after 5 days of 40% overfeeding of both a HC (20% fat, 60% CHO) diet and a HF (50% fat, 30% CHO) diet. At the end of each diet phase, in vivo insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp technique. Ex vivo insulin action was measured from skeletal muscle tissue samples obtained 15 minutes after insulin infusion was initiated.

Results
Overall there was no change in whole-body insulin sensitivity as measured by glucose disposal rate (GDR, EC: 12.1 ± 4.7; HC: 10.9 ± 2.7; HF: 10.8 ± 3.4). Assessment of skeletal muscle insulin signaling demonstrated increased tyrosine phosphorylation of IRS-1 (p < 0.001) and increased IRS-1-associated phosphatidylinositol 3 (PI 3)-kinase activity (p < 0.001) following HC overfeeding. In contrast, HF overfeeding increased skeletal muscle serine phosophorylation of IRS-1 (p < 0.001) and increased total expression of p85α (P < 0.001).

Conclusion
We conclude that acute bouts of overnutrition lead to changes at the cellular level before whole-body insulin sensitivity is altered. On a signaling level, HC overfeeding resulted in changes compatible with increased insulin sensitivity. In contrast, molecular changes in HF overfeeding were compatible with a reduced insulin sensitivity.

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ollie wrote:Nu would love it. Source?

Dtlv74 wrote:I have another related scientific article which again suggests obesity and overeating is the prime issue with insulin insensitivity not so much carbs on their own. It also suggests that a diet heavy with long chain fatty acids (saturated fats) causes more problems due to increased lipotoxicity and ceramide production which interferes further with insulin reponses.

Pain wrote:I've stated the principles in that study before (only to have them 'rubbished' by nu!)
Thanks for that study, it backs up some of my theory.

Dtlv74 wrote:I have another related scientific article which again suggests obesity and overeating is the prime issue with insulin insensitivity not so much carbs on their own. It also suggests that a diet heavy with long chain fatty acids (saturated fats) causes more problems due to increased lipotoxicity and ceramide production which interferes further with insulin reponses.

Bingo.

Resurrected wrote:

Pain wrote:I've stated the principles in that study before (only to have them 'rubbished' by nu!)
Thanks for that study, it backs up some of my theory.

Dtlv74 wrote:I have another related scientific article which again suggests obesity and overeating is the prime issue with insulin insensitivity not so much carbs on their own. It also suggests that a diet heavy with long chain fatty acids (saturated fats) causes more problems due to increased lipotoxicity and ceramide production which interferes further with insulin reponses.

Bingo.

Have you got your nuts off yet and unloaded your man sack into a silk purse? Or are you still as untouched as the day you were born?

health4ni wrote:is it ALL saturated fats or just the bad ones?

health4ni wrote:is it ALL saturated fats or just the bad ones?

Pain wrote:
Have you got your nuts off yet and unloaded your man sack into a silk purse? Or are you still as untouched as the day you were born?