Lipotoxicity: How Saturated Fat Raises Blood Sugar

Lipotoxicity: How Saturated Fat Raises Blood Sugar
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The reason those eating plant-based diets have less fat buildup in their muscle cells and less insulin resistance may be because saturated fats appear to impair blood sugar control the most.

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The association between fat and insulin resistance is now widely accepted–so-called ectopic fat accumulation–the accumulation of fat in places it’s not supposed to be, like within our muscle cells. But not all fats affect muscles the same. The type of fat–saturated or unsaturated–is critical. Saturated fats like palmitate, found mostly in meat, dairy, and eggs, cause insulin resistance, but oleate, found mostly in nuts, olives, and avocados may actually improve insulin sensitivity. What makes saturated fat bad? Saturated fat causes more of those toxic breakdown products and mitochondrial dysfunction, and increases oxidative stress, free radicals, and inflammation, establishing a vicious cycle of events in which saturated fat-induced free radicals cause dysfunction in the little power plants within our muscle cells, which causes an increase in free radical production and the impairment of insulin signaling.

Fat cells filled with saturated fat activate an inflammatory response to a far greater extent. This increased inflammation, along with eating more saturated fat, has been demonstrated to raise insulin resistance through free radical and ceramide production. Saturated fat has also been shown to have a direct effect on skeletal muscle insulin resistance. Accumulation of saturated fat increases the amount of diacylglycerol in the muscles, which has been demonstrated to have a potent effect on muscle insulin resistance. It doesn’t matter if the fat in our blood comes from our own fat, or from their fat.

You can take muscle biopsies from people and correlate the saturated fat buildup in their muscles with insulin resistance.

While monounsaturated fats are more likely to be detoxified or safely stored away, saturated fats create these toxic breakdown products, like ceramide, that cause lipotoxicity. Lipo- meaning fat, as in liposuction, and toxicity. This fat toxicity in our muscles is a well-known concept in the explanation of the trigger for insulin resistance.

I’ve talked about the role saturated and trans fats contribute to the progression of other diseases, like autoimmune diseases, cancer, and heart disease, but they can also cause insulin resistance, the underlying cause of prediabetes and type 2 diabetes. In the human diet, saturated fats are derived from animal sources while trans fats originate in meat and milk, in addition to partially hydrogenated and refined vegetable oils.

That’s why experimentally shifting people from animal fats to plant fats can improve insulin sensitivity. Insulin sensitivity was impaired on the diet with added butterfat, but not on the diet with added olive fat.

We know prolonged exposure of our muscles to high levels of fat leads to severe insulin resistance, with saturated fats demonstrated to be the worst. But they don’t just lead to inhibition of insulin signaling, the activation of inflammatory pathways, and the increase in free radicals. They cause an alteration in gene expression, leading to a suppression of key mitochondrial enzymes, like carnitine palmitoyltransferase–which finally solves the mystery of why those eating vegetarian have a 60% higher expression of that fat-burning enzyme. They’re eating less saturated fat.

So do those eating plant-based diets have less fat clogging their muscles and less insulin resistance too? There hasn’t been any data available regarding the insulin sensitivity or inside-muscle cell-fat of those eating vegan or vegetarian, until now.

Researchers at the Imperial College of London compared the insulin resistance and muscle fat of vegans versus omnivores. Now those eating plant-based diets have the unfair advantage of being so much slimmer, so they found omnivores who were as skinny as vegans to see if plant-based diets had a direct benefit, as opposed to indirectly pulling fat out of the muscles by helping people lose weight in general.

They found significantly less fat trapped in the muscle cells of vegans compared to omnivores even at the same body weight. They found better insulin sensitivity, better blood sugar levels, better insulin levels, and, excitingly, significantly improved beta-cell function–the cells in the pancreas that make insulin in the first place. They conclude that eating vegan is not only expected to be cardioprotective, helping prevent our #1 killer–heart disease–but that veganism may be beta cell protective as well, helping also to prevent our seventh leading cause of death–diabetes.

To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.

Please consider volunteering to help out on the site.

Images thanks to Djjewelz and Max Westby via Flickr, Kapa65 and WaltiGoehner via Pixabay, and Ljupco Smokovski via 123RF.

The association between fat and insulin resistance is now widely accepted–so-called ectopic fat accumulation–the accumulation of fat in places it’s not supposed to be, like within our muscle cells. But not all fats affect muscles the same. The type of fat–saturated or unsaturated–is critical. Saturated fats like palmitate, found mostly in meat, dairy, and eggs, cause insulin resistance, but oleate, found mostly in nuts, olives, and avocados may actually improve insulin sensitivity. What makes saturated fat bad? Saturated fat causes more of those toxic breakdown products and mitochondrial dysfunction, and increases oxidative stress, free radicals, and inflammation, establishing a vicious cycle of events in which saturated fat-induced free radicals cause dysfunction in the little power plants within our muscle cells, which causes an increase in free radical production and the impairment of insulin signaling.

Fat cells filled with saturated fat activate an inflammatory response to a far greater extent. This increased inflammation, along with eating more saturated fat, has been demonstrated to raise insulin resistance through free radical and ceramide production. Saturated fat has also been shown to have a direct effect on skeletal muscle insulin resistance. Accumulation of saturated fat increases the amount of diacylglycerol in the muscles, which has been demonstrated to have a potent effect on muscle insulin resistance. It doesn’t matter if the fat in our blood comes from our own fat, or from their fat.

You can take muscle biopsies from people and correlate the saturated fat buildup in their muscles with insulin resistance.

While monounsaturated fats are more likely to be detoxified or safely stored away, saturated fats create these toxic breakdown products, like ceramide, that cause lipotoxicity. Lipo- meaning fat, as in liposuction, and toxicity. This fat toxicity in our muscles is a well-known concept in the explanation of the trigger for insulin resistance.

I’ve talked about the role saturated and trans fats contribute to the progression of other diseases, like autoimmune diseases, cancer, and heart disease, but they can also cause insulin resistance, the underlying cause of prediabetes and type 2 diabetes. In the human diet, saturated fats are derived from animal sources while trans fats originate in meat and milk, in addition to partially hydrogenated and refined vegetable oils.

That’s why experimentally shifting people from animal fats to plant fats can improve insulin sensitivity. Insulin sensitivity was impaired on the diet with added butterfat, but not on the diet with added olive fat.

We know prolonged exposure of our muscles to high levels of fat leads to severe insulin resistance, with saturated fats demonstrated to be the worst. But they don’t just lead to inhibition of insulin signaling, the activation of inflammatory pathways, and the increase in free radicals. They cause an alteration in gene expression, leading to a suppression of key mitochondrial enzymes, like carnitine palmitoyltransferase–which finally solves the mystery of why those eating vegetarian have a 60% higher expression of that fat-burning enzyme. They’re eating less saturated fat.

So do those eating plant-based diets have less fat clogging their muscles and less insulin resistance too? There hasn’t been any data available regarding the insulin sensitivity or inside-muscle cell-fat of those eating vegan or vegetarian, until now.

Researchers at the Imperial College of London compared the insulin resistance and muscle fat of vegans versus omnivores. Now those eating plant-based diets have the unfair advantage of being so much slimmer, so they found omnivores who were as skinny as vegans to see if plant-based diets had a direct benefit, as opposed to indirectly pulling fat out of the muscles by helping people lose weight in general.

They found significantly less fat trapped in the muscle cells of vegans compared to omnivores even at the same body weight. They found better insulin sensitivity, better blood sugar levels, better insulin levels, and, excitingly, significantly improved beta-cell function–the cells in the pancreas that make insulin in the first place. They conclude that eating vegan is not only expected to be cardioprotective, helping prevent our #1 killer–heart disease–but that veganism may be beta cell protective as well, helping also to prevent our seventh leading cause of death–diabetes.

To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.

Please consider volunteering to help out on the site.

Images thanks to Djjewelz and Max Westby via Flickr, Kapa65 and WaltiGoehner via Pixabay, and Ljupco Smokovski via 123RF.

Doctor's Note

This is the third of a three-part series, starting with What Causes Insulin Resistance? and The Spillover Effect Links Obesity to Diabetes. I wish I could have fit it all into one video, but it would have just been too long.

Even if saturated fat weren’t associated with heart disease, its effects on pancreatic function and insulin resistance in the muscles would be enough to warrant avoiding it. Despite popular press accounts, saturated fat intake remains the primary modifiable determinant of LDL cholesterol, the #1 risk factor for our #1 killer–heart disease. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

How low should we shoot for in terms of saturated fat intake? As low as possible, according to the U.S. National Academies of Science Institute of Medicine: Trans Fat, Saturated Fat, and Cholesterol: Tolerable Upper Intake of Zero.

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