The Carb-Sane Asylum

Lots of buzz over mitochondria of late.  So I thought I'd share this find: High-fat diets cause insulin resistance despite an increase in muscle mitochondria It has been hypothesized that insulin resistance is mediated by a deficiency of mitochondria in skeletal muscle. In keeping with this hypothesis, high-fat diets that cause insulin resistance have been reported to result in a decrease in muscle mitochondria.    In contrast, we found that feeding rats high-fat diets that cause muscle insulin resistance results in a concomitant gradual increase in muscle mitochondria.

Free Fatty Acids and Cytokines Induce Pancreatic ß-Cell Apoptosis by Different Mechanisms (I've scrubbed the distracting reference numbers from some excerpts of the introduction and I'm also going to try to cite only the information pertinent to T2) Hypercaloric diets containing large amounts of fat, also called the Western diet, contribute to a major extent to the increasing prevalence of obesity and type 2 diabetes mellitus (T2DM). T2DM is characterized by peripheral insulin resistance, pancreatic ß-cell dysfunction, and decreased ß-cell mass associated with increased rates of ß-cell apoptosis. Elevated levels of circulating free fatty acids (FFAs) contribute to the pathogenesis of T2DM. High concentrations of FFAs lead to both impairment of insulin action and ß-cell dysfunction.  Moreover, FFAs have been shown to cause ß -cell death, mainly by apoptosis.  Of note, increased adiposity is associated not only with increa...

As many of my readers know, I've been challenged lately on my beliefs on NEFA.  So I thought I would summarize my thinking on this in a post rather than having several comments scattered amongst a few threads.   I'm not going to be referencing my post here at this time (it's too time consuming to do so at the moment).  If/when I have the opportunity to do so in the future, I'll do a bumped update.   These are my thoughts based on extensive research of the peer review literature on this topic, in almost all cases, considered review of full text articles including reading as many supporting citations in major reviews as possible.  Over the past year I have read at least a hundred such articles. Elevated non-esterified or free fatty acids (NEFA/FFA) are a symptom associated with insulin resistance, Metabolic Syndrome (aka Syndrome X) and Type II diabetes.  The overwhelming evidence in the literature points to elevated NEFA being more than just associated wit...

This post may well make heads spin.  It sure did mine. A common claim in LC circles is that we "waste" excess fats through futile cycling.  Although this has not been demonstrated in any significant amount in humans except in massive fat overfeeding, it is still incorporated into books and blog posts by the likes of Dr. Mike Eades (futile cycling to "blow off" low carb excesses is stated as if fact in The 6 Week Cure). Inherent in these statements is the implication that this only happens for excess dietary fat when carbs are low ... insulin would be trapping the fats in the cells as the theories go.  Well ... Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity   (2004 Review Article,  PDF)

Comparative toxicity of fatty acids on a macrophage cell line (J774) In the present study, the cytotoxicity of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on a macrophage cell line (J774) was investigated. The induction of toxicity was investigated by changes in cell size, granularity, membrane integrity, DNA fragmentation and phosphatidylserine externalization by using flow cytometry. Fluorescence microscopy was used to determine the type of cell death (Acridine Orange/ethidium bromide assay). The possible mechanisms involved were examined by measuring mitochondrial depolarization, lipid accumulation and PPARγ (peroxisome-proliferator-activated receptor γ ) activation. The results demonstrate that fatty acids induce apoptosis and necrosis of J774 cells. At high concentrations, fatty acids cause macrophage death mainly by necrosis. The cytotoxicity of the fatty acids was not strictly related ...

Just some musings on carbohydrates and fats, but with a scientific basis so put it here. Personally I believe the obesity epidemic can be blamed primarily on two phenomena: 1.  The abundance of high calorie foods high in fats & carbs (I'll call them CF) in ever larger portions, and 2.  Liquid calories loaded with sugar and/or fat To prevent obesity my solution is simple:  Keep the fats and carbs separate.  If you're going to eat carbohydrate, eat it with lean protein and/or in whole form so you get sufficient fiber.  Go easy on the fat.  If you're going to eat fat, chances are it is attached to protein, forgo the carbs.  If you simply must eat CF foods, rely on portion control/calorie counting and not on satiety to determine how much you eat.  Keep the total caloric load low, perhaps in the 2-300 cal range, to keep the unnatural assault on your metabolism to a minimum.   My reasons for this are twofold: 1.  Our paleolithic ances...

Fat storage in pancreas and in insulin-sensitive tissues in pathogenesis of type 2 diabetes Obesity is associated with increased storage of lipids in nonadipose tissues like skeletal muscle, liver, and pancreatic b cells. These lipids constitute a continuous source of long-chain fatty acyl CoA (LC-CoA) and derived metabolites like diacylglycerol and ceramide, acting as signalling molecules on protein kinases activities (in particular, the family of PKCs), ion channel, gene expression, and protein acylation. In skeletal muscle, the increase in LC-CoA and diacylglycerol translocates and activates specific protein kinase C (PKC) isoforms, which will phosphorylate IRS-1 on serine, preventing its phosphorylation on tyrosine and association with PI3 kinase. This interrupts the insulin signalling pathway leading to the stimulation of glucose transport. In pancreatic b cells, short-term excess of fatty acids or LC-CoA activates PKC and also directly stimulates insulin exocytosis. Longterm ex...

Vascular function, insulin resistance and fatty acids   (I'll blog on the vascular focus of this paper shortly, but this post is focusing on the bolded statements in the abstract). Abstract Over the past 10 years it has become clear that intact vascular function, especially at the level of the endothelium {cells lining the blood vessels}, is paramount in the prevention or delay of cardiovascular disease. It has also become clear that insulin itself, in addition to its metabolic actions, directly effects vascular endothelium and smooth muscle.  Insulin, at normal physiologic concentrations, causes changes in skeletal muscle blood flow in healthy, insulin-sensitive subjects. Insulin’s effect on the endothelium is mediated through its own receptor and insulin signalling pathways, resulting in the increased release of nitric oxide. Insulin’s vascular actions are impaired in insulin-resistant conditions such as obesity...

Thanks to reader Cody for finding a study I had come across previously regarding IMCL/IMTG.  Actually the study linked to was an update, but there's a secondary lesson, I believe, to be had from the results.  Since this was a study in older folks, there's a sub-message here:  it's never too late! Study:   Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete’s paradox revisited We previously reported an “athlete’s paradox” in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content. The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle, and insulin sensitivity in previously sedentary overweight to obese, insulin- resistant, older subjects. Twenty-five older (66.4 0.8 yr) obese (BMI 30.3 0.7 kg/m2) men (n 9...