Leptin is a major hormone regulator of fat mass in vertebrates. It's a frequent topic on this blog because I believe it's central to overweight and modern metabolic disorders. Here's how it works. Leptin is secreted by fat tissue, and its blood levels are proportional to fat mass. The more fat tissue, the more leptin. Leptin reduces appetite, increases fat release from fat tissue and increases the metabolic rate. Normally, this creates a "feedback loop" that keeps fat mass within a fairly narrow range. Any increase in fat tissue causes an increase in leptin, which burns fat tissue at an accelerated rate. This continues until fat mass has decreased enough to return leptin to its original level.
Leptin was first identified through research on the "obese" mutant mouse. The obese strain arose by a spontaneous mutation, and is extremely fat. The mutation turned out to be in a protein investigators dubbed leptin. When researchers first discovered leptin, they speculated that it could be the "obesity gene", and supplemental leptin a potential treatment for obesity. They later discovered (to their great chagrin) that obese people produce much more leptin than thin people, so a defeciency of leptin was clearly not the problem, as it was in the obese mouse. They subsequently found that obese people scarcely respond to injected leptin by reducing their food intake, as thin people do. They are leptin resistant. This makes sense if you think about it. The only way a person can gain significant fat mass is if the leptin feedback loop isn't working correctly.
Another rodent model of leptin resistance arose later, the "Zucker fatty" rat. Zucker rats have a mutation in the leptin receptor gene. They secrete leptin just fine, but they don't respond to it because they have no functional receptor. This makes them an excellent model of complete leptin resistance. What happens to Zucker rats? They become obese, hypometabolic, hyperphagic, hypertensive, insulin resistant, and they develop blood lipid disturbances. It should sound familiar; it's the metabolic syndrome and it affects 24% of Americans (CDC NHANES III). Guess what's the first symptom of impending metabolic syndrome in humans, even before insulin resistance and obesity? Leptin resistance. This makes leptin an excellent contender for the keystone position in overweight and other metabolic disorders.
I've mentioned before that the two most commonly used animal models of the metabolic syndrome are both sugar-fed rats. Fructose, which accounts for 50% of table sugar and 55% of high-fructose corn syrup, is probably the culprit. Glucose, which is the remainder of table sugar and high-fructose corn syrup, and the product of starch digestion, does not have the same effects. I think it's also relevant that refined sugar contains no vitamins or minerals whatsoever. Sweetener consumption in the U.S. has increased from virtually nothing in 1850, to 84 pounds per year in 1909, to 119 pounds in 1970, to 142 pounds in 2005 (source).
In a recent paper, Dr. Philip Scarpace's group (in collaboration with Dr. Richard Johnson), showed that a high-fructose diet causes leptin resistance in rats. The diet was 60% fructose, which is extreme by any standards, but it caused a complete resistance to the effect of leptin on food intake. Normally, leptin binds receptors in a brain region called the hypothalamus, which is responsible for food intake behaviors (including in humans). This accounts for leptin's ability to reduce food consumption. Fructose-fed rats did not reduce their food intake at all when injected with leptin, while rats on a normal diet did. When subsequently put on a high-fat diet (60% lard), rats that started off on the fructose diet gained more weight.
I think it's worth mentionong that rodents don't respond to high-fat diets in the same way as humans, as judged by the efficacy of low-carbohydrate diets for weight loss. Industrial lard also has a very poor ratio of omega-6 to omega-3 fats (especially if it's hydrogenated), which may also contribute to the observed weight gain.
Fructose-fed rats had higher cholesterol and twice the triglycerides of control-fed rats. Fructose increases triglycerides because it goes straight to the liver, which makes it into fat that's subsequently exported into the bloodstream. Elevated triglycerides impair leptin transport from the blood to the hypothalamus across the blood-brain barrier, which separates the central nervous system from the rest of the body. Fructose also impaired the response of the hypothalamus to the leptin that did reach it. Both effects may contribute to the leptin resistance Dr. Scarpace's group observed.
Just four weeks of fructose feeding in humans (1.5g per kg body weight) increased leptin levels by 48%. Body weight did not change during the study, indicating that more leptin was required to maintain the same level of fat mass. This may be the beginning of leptin resistance.
Leptin Resistance and Sugar
Leptin is a major hormone regulator of fat mass in vertebrates. It's a frequent topic on this blog because I believe it's central to overweight and modern metabolic disorders. Here's how it works. Leptin is secreted by fat tissue, and its blood levels are proportional to fat mass. The more fat tissue, the more leptin. Leptin reduces appetite, increases fat release from fat tissue and increases the metabolic rate. Normally, this creates a "feedback loop" that keeps fat mass within a fairly narrow range. Any increase in fat tissue causes an increase in leptin, which burns fat tissue at an accelerated rate. This continues until fat mass has decreased enough to return leptin to its original level.
Leptin was first identified through research on the "obese" mutant mouse. The obese strain arose by a spontaneous mutation, and is extremely fat. The mutation turned out to be in a protein investigators dubbed leptin. When researchers first discovered leptin, they speculated that it could be the "obesity gene", and supplemental leptin a potential treatment for obesity. They later discovered (to their great chagrin) that obese people produce much more leptin than thin people, so a defeciency of leptin was clearly not the problem, as it was in the obese mouse. They subsequently found that obese people scarcely respond to injected leptin by reducing their food intake, as thin people do. They are leptin resistant. This makes sense if you think about it. The only way a person can gain significant fat mass is if the leptin feedback loop isn't working correctly.
Another rodent model of leptin resistance arose later, the "Zucker fatty" rat. Zucker rats have a mutation in the leptin receptor gene. They secrete leptin just fine, but they don't respond to it because they have no functional receptor. This makes them an excellent model of complete leptin resistance. What happens to Zucker rats? They become obese, hypometabolic, hyperphagic, hypertensive, insulin resistant, and they develop blood lipid disturbances. It should sound familiar; it's the metabolic syndrome and it affects 24% of Americans (CDC NHANES III). Guess what's the first symptom of impending metabolic syndrome in humans, even before insulin resistance and obesity? Leptin resistance. This makes leptin an excellent contender for the keystone position in overweight and other metabolic disorders.
I've mentioned before that the two most commonly used animal models of the metabolic syndrome are both sugar-fed rats. Fructose, which accounts for 50% of table sugar and 55% of high-fructose corn syrup, is probably the culprit. Glucose, which is the remainder of table sugar and high-fructose corn syrup, and the product of starch digestion, does not have the same effects. I think it's also relevant that refined sugar contains no vitamins or minerals whatsoever. Sweetener consumption in the U.S. has increased from virtually nothing in 1850, to 84 pounds per year in 1909, to 119 pounds in 1970, to 142 pounds in 2005 (source).
In a recent paper, Dr. Philip Scarpace's group (in collaboration with Dr. Richard Johnson), showed that a high-fructose diet causes leptin resistance in rats. The diet was 60% fructose, which is extreme by any standards, but it caused a complete resistance to the effect of leptin on food intake. Normally, leptin binds receptors in a brain region called the hypothalamus, which is responsible for food intake behaviors (including in humans). This accounts for leptin's ability to reduce food consumption. Fructose-fed rats did not reduce their food intake at all when injected with leptin, while rats on a normal diet did. When subsequently put on a high-fat diet (60% lard), rats that started off on the fructose diet gained more weight.
I think it's worth mentionong that rodents don't respond to high-fat diets in the same way as humans, as judged by the efficacy of low-carbohydrate diets for weight loss. Industrial lard also has a very poor ratio of omega-6 to omega-3 fats (especially if it's hydrogenated), which may also contribute to the observed weight gain.
Fructose-fed rats had higher cholesterol and twice the triglycerides of control-fed rats. Fructose increases triglycerides because it goes straight to the liver, which makes it into fat that's subsequently exported into the bloodstream. Elevated triglycerides impair leptin transport from the blood to the hypothalamus across the blood-brain barrier, which separates the central nervous system from the rest of the body. Fructose also impaired the response of the hypothalamus to the leptin that did reach it. Both effects may contribute to the leptin resistance Dr. Scarpace's group observed.
Just four weeks of fructose feeding in humans (1.5g per kg body weight) increased leptin levels by 48%. Body weight did not change during the study, indicating that more leptin was required to maintain the same level of fat mass. This may be the beginning of leptin resistance.
Leptin was first identified through research on the "obese" mutant mouse. The obese strain arose by a spontaneous mutation, and is extremely fat. The mutation turned out to be in a protein investigators dubbed leptin. When researchers first discovered leptin, they speculated that it could be the "obesity gene", and supplemental leptin a potential treatment for obesity. They later discovered (to their great chagrin) that obese people produce much more leptin than thin people, so a defeciency of leptin was clearly not the problem, as it was in the obese mouse. They subsequently found that obese people scarcely respond to injected leptin by reducing their food intake, as thin people do. They are leptin resistant. This makes sense if you think about it. The only way a person can gain significant fat mass is if the leptin feedback loop isn't working correctly.
Another rodent model of leptin resistance arose later, the "Zucker fatty" rat. Zucker rats have a mutation in the leptin receptor gene. They secrete leptin just fine, but they don't respond to it because they have no functional receptor. This makes them an excellent model of complete leptin resistance. What happens to Zucker rats? They become obese, hypometabolic, hyperphagic, hypertensive, insulin resistant, and they develop blood lipid disturbances. It should sound familiar; it's the metabolic syndrome and it affects 24% of Americans (CDC NHANES III). Guess what's the first symptom of impending metabolic syndrome in humans, even before insulin resistance and obesity? Leptin resistance. This makes leptin an excellent contender for the keystone position in overweight and other metabolic disorders.
I've mentioned before that the two most commonly used animal models of the metabolic syndrome are both sugar-fed rats. Fructose, which accounts for 50% of table sugar and 55% of high-fructose corn syrup, is probably the culprit. Glucose, which is the remainder of table sugar and high-fructose corn syrup, and the product of starch digestion, does not have the same effects. I think it's also relevant that refined sugar contains no vitamins or minerals whatsoever. Sweetener consumption in the U.S. has increased from virtually nothing in 1850, to 84 pounds per year in 1909, to 119 pounds in 1970, to 142 pounds in 2005 (source).
In a recent paper, Dr. Philip Scarpace's group (in collaboration with Dr. Richard Johnson), showed that a high-fructose diet causes leptin resistance in rats. The diet was 60% fructose, which is extreme by any standards, but it caused a complete resistance to the effect of leptin on food intake. Normally, leptin binds receptors in a brain region called the hypothalamus, which is responsible for food intake behaviors (including in humans). This accounts for leptin's ability to reduce food consumption. Fructose-fed rats did not reduce their food intake at all when injected with leptin, while rats on a normal diet did. When subsequently put on a high-fat diet (60% lard), rats that started off on the fructose diet gained more weight.
I think it's worth mentionong that rodents don't respond to high-fat diets in the same way as humans, as judged by the efficacy of low-carbohydrate diets for weight loss. Industrial lard also has a very poor ratio of omega-6 to omega-3 fats (especially if it's hydrogenated), which may also contribute to the observed weight gain.
Fructose-fed rats had higher cholesterol and twice the triglycerides of control-fed rats. Fructose increases triglycerides because it goes straight to the liver, which makes it into fat that's subsequently exported into the bloodstream. Elevated triglycerides impair leptin transport from the blood to the hypothalamus across the blood-brain barrier, which separates the central nervous system from the rest of the body. Fructose also impaired the response of the hypothalamus to the leptin that did reach it. Both effects may contribute to the leptin resistance Dr. Scarpace's group observed.
Just four weeks of fructose feeding in humans (1.5g per kg body weight) increased leptin levels by 48%. Body weight did not change during the study, indicating that more leptin was required to maintain the same level of fat mass. This may be the beginning of leptin resistance.
The Fundamentals
I heard an interview of Michael Pollan yesterday on Talk of the Nation. He made some important points about nutrition that bear repeating. He's fond of saying "don't eat anything your grandmother wouldn't recognize as food". That doesn't mean your grandmother specifically, but anyone's grandmother, whether she was Japanese, American or African. The point is that commercial food processing has taken us away from the foods, and traditional food preparation methods, on which our bodies evolved to thrive. At this point, we don't know enough about health to design a healthy synthetic diet. Diet and health are too complex for reductionism at our current level of understanding. For that reason, any departure from natural foods and traditional food processing techniques is suspect.
Mainstream nutrition science has repeatedly contradicted itself and led us down the wrong path. This means that traditional cultures still have something to teach us about health. Hunter-gatherers and certain other non-industrial cultures are still the healthiest people on Earth, from the perspective of non-communicable disease. Pollan used the example of butter. First we thought it was healthy, then we were told it contains too much saturated fat and should be replaced with hydrogenated vegetable margarine. Now we learn that trans fats are unhealthy, so we're making new margarines that are low in trans fats, but are still industrially processed pseudo-foods. How long will it take to show these new fats are harmful? What will be the next industrial fat to replace them? This game can be played forever as the latest unproven processed food replaces the previous one, and it will never result in something as healthy as real butter.
The last point of Pollan's I'll mention is that the world contains (or contained) a diversity of different cultures, living in dramatically different ways, many of which do not suffer from degenerative disease. These range from carnivores like the Inuit, to plant-heavy agriculturalists like the Kitavans, to pastoralists like the Masai. The human body is adapted to a wide variety of foodways, but the one it doesn't seem to like is the modern Western diet.
Pollan's new book is In Defense of Food. I haven't read it, but I think it would be a good introduction to the health, ethical and environmental issues that surround food choices. He's a clear and accessible writer.
Merry Christmas, happy Hanukkah, and happy holidays to everyone!
Mainstream nutrition science has repeatedly contradicted itself and led us down the wrong path. This means that traditional cultures still have something to teach us about health. Hunter-gatherers and certain other non-industrial cultures are still the healthiest people on Earth, from the perspective of non-communicable disease. Pollan used the example of butter. First we thought it was healthy, then we were told it contains too much saturated fat and should be replaced with hydrogenated vegetable margarine. Now we learn that trans fats are unhealthy, so we're making new margarines that are low in trans fats, but are still industrially processed pseudo-foods. How long will it take to show these new fats are harmful? What will be the next industrial fat to replace them? This game can be played forever as the latest unproven processed food replaces the previous one, and it will never result in something as healthy as real butter.
The last point of Pollan's I'll mention is that the world contains (or contained) a diversity of different cultures, living in dramatically different ways, many of which do not suffer from degenerative disease. These range from carnivores like the Inuit, to plant-heavy agriculturalists like the Kitavans, to pastoralists like the Masai. The human body is adapted to a wide variety of foodways, but the one it doesn't seem to like is the modern Western diet.
Pollan's new book is In Defense of Food. I haven't read it, but I think it would be a good introduction to the health, ethical and environmental issues that surround food choices. He's a clear and accessible writer.
Merry Christmas, happy Hanukkah, and happy holidays to everyone!
The Fundamentals
I heard an interview of Michael Pollan yesterday on Talk of the Nation. He made some important points about nutrition that bear repeating. He's fond of saying "don't eat anything your grandmother wouldn't recognize as food". That doesn't mean your grandmother specifically, but anyone's grandmother, whether she was Japanese, American or African. The point is that commercial food processing has taken us away from the foods, and traditional food preparation methods, on which our bodies evolved to thrive. At this point, we don't know enough about health to design a healthy synthetic diet. Diet and health are too complex for reductionism at our current level of understanding. For that reason, any departure from natural foods and traditional food processing techniques is suspect.
Mainstream nutrition science has repeatedly contradicted itself and led us down the wrong path. This means that traditional cultures still have something to teach us about health. Hunter-gatherers and certain other non-industrial cultures are still the healthiest people on Earth, from the perspective of non-communicable disease. Pollan used the example of butter. First we thought it was healthy, then we were told it contains too much saturated fat and should be replaced with hydrogenated vegetable margarine. Now we learn that trans fats are unhealthy, so we're making new margarines that are low in trans fats, but are still industrially processed pseudo-foods. How long will it take to show these new fats are harmful? What will be the next industrial fat to replace them? This game can be played forever as the latest unproven processed food replaces the previous one, and it will never result in something as healthy as real butter.
The last point of Pollan's I'll mention is that the world contains (or contained) a diversity of different cultures, living in dramatically different ways, many of which do not suffer from degenerative disease. These range from carnivores like the Inuit, to plant-heavy agriculturalists like the Kitavans, to pastoralists like the Masai. The human body is adapted to a wide variety of foodways, but the one it doesn't seem to like is the modern Western diet.
Pollan's new book is In Defense of Food. I haven't read it, but I think it would be a good introduction to the health, ethical and environmental issues that surround food choices. He's a clear and accessible writer.
Merry Christmas, happy Hanukkah, and happy holidays to everyone!
Mainstream nutrition science has repeatedly contradicted itself and led us down the wrong path. This means that traditional cultures still have something to teach us about health. Hunter-gatherers and certain other non-industrial cultures are still the healthiest people on Earth, from the perspective of non-communicable disease. Pollan used the example of butter. First we thought it was healthy, then we were told it contains too much saturated fat and should be replaced with hydrogenated vegetable margarine. Now we learn that trans fats are unhealthy, so we're making new margarines that are low in trans fats, but are still industrially processed pseudo-foods. How long will it take to show these new fats are harmful? What will be the next industrial fat to replace them? This game can be played forever as the latest unproven processed food replaces the previous one, and it will never result in something as healthy as real butter.
The last point of Pollan's I'll mention is that the world contains (or contained) a diversity of different cultures, living in dramatically different ways, many of which do not suffer from degenerative disease. These range from carnivores like the Inuit, to plant-heavy agriculturalists like the Kitavans, to pastoralists like the Masai. The human body is adapted to a wide variety of foodways, but the one it doesn't seem to like is the modern Western diet.
Pollan's new book is In Defense of Food. I haven't read it, but I think it would be a good introduction to the health, ethical and environmental issues that surround food choices. He's a clear and accessible writer.
Merry Christmas, happy Hanukkah, and happy holidays to everyone!
U.S. Weight, Lifestyle and Diet Trends, 1970- 2007
For this post, I compiled statistics on U.S. weight, health and lifestyle trends, and graphed them as consistently as possible. They span the period from 1970 to 2007, during which the obesity rate doubled. The data come from the National Health and Nutrition Examination Survey (NHANES), the Behavioral Risk Factor Surveillance System (BRFSS), and the U.S. Department of Agriculture (USDA). Some of the graphs are incomplete, either because the data don't exist, or because I wasn't able to find them. 
Obesity is defined as a body mass index (BMI) of 30+; overweight is a BMI of 25+. Yes, it's frightening. It has affected adults and children (NHANES).
The percentage of Americans who report exercising in their spare time has actually increased since 1988 (BRFSS).
We're eating about 250 more calories per day, according to NHANES.
The 250 extra calories are coming from carbohydrate (NHANES).
We're eating more vegetables and fruit (USDA).
We're eating more meat by weight, although calories from meat have probably gone down because the meat has gotten leaner (USDA). This graph represents red meat, fish and poultry. The increase comes mostly from poultry. Boneless, skinless chicken breasts anyone?
We're eating more sugar (USDA). The scale of the graph doesn't allow you to fully appreciate that sweetener consumption had increased by a full 100 calories per day by 1999, although it has dropped a bit since then. This is based on food disappearance data. In other words, the amount consumed is estimated using the amount sold domestically, minus a percentage that approximates waste. High-fructose corn syrup has seized nearly 50% of the sweetener market since 1970.
Again, the scale of the graph doesn't allow you to fully appreciate the magnitude of the change here. In 2000, we ate approximately 2.5 ounces, or 280 calories, more processed grains per day than in 1970 (USDA). That has since decreased slightly (34 calories). You might be saying to yourself right now "hey, that plus the 100 calories from sugar adds up to more of an increase than the NHANES data show!" Yes, and I think that points to the fact that the data sets are not directly comparable. NHANES data are self-reported whereas USDA data are collected from vendors. Regardless of the absolute numbers, our processed grain consumption has gone way up since 1970.
Wheat is still king. Although we grow a lot of corn in this country, most of it gets fed to animals. We prefer eating wheat without first feeding it to an intermediary. In absolute quantity, wheat consumption has increased more than any other grain (not including corn syrup).
Bye bye whole milk. Hello skim milk (USDA).
This graph represents "added fats", as opposed to fats that occur naturally in meat or milk (the USDA does not track the latter). Added fats include salad oil, cooking oil, deep fry oil, butter, lard, tallow, etc. We are eating a lot more vegetable oil than we were in 1970. It comes chiefly from the industrial, omega-6 rich oils such as soybean, corn and canola. Added animal fats have increased slightly, but it's pretty insignificant in terms of calories.
There is an artifact in this graph that I have to point out. In 2000, the USDA changed the way it gathered vegetable oil data. This led to an abrupt, apparent increase in its consumption that is obvious on the graph. So it's difficult to make any quantitative conclusions, but I think it's clear nevertheless that vegetable oil intake has increased considerably.
Between 1970 and 1980, something changed in the U.S. that caused a massive increase in obesity and other health problems. Some combination of factors reached a critical mass that our metabolism could no longer tolerate. The three biggest changes in the American diet since 1970:
Obesity is defined as a body mass index (BMI) of 30+; overweight is a BMI of 25+. Yes, it's frightening. It has affected adults and children (NHANES).
The percentage of Americans who report exercising in their spare time has actually increased since 1988 (BRFSS).
We're eating about 250 more calories per day, according to NHANES.
The 250 extra calories are coming from carbohydrate (NHANES).
We're eating more vegetables and fruit (USDA).
We're eating more meat by weight, although calories from meat have probably gone down because the meat has gotten leaner (USDA). This graph represents red meat, fish and poultry. The increase comes mostly from poultry. Boneless, skinless chicken breasts anyone?
We're eating more sugar (USDA). The scale of the graph doesn't allow you to fully appreciate that sweetener consumption had increased by a full 100 calories per day by 1999, although it has dropped a bit since then. This is based on food disappearance data. In other words, the amount consumed is estimated using the amount sold domestically, minus a percentage that approximates waste. High-fructose corn syrup has seized nearly 50% of the sweetener market since 1970.
Again, the scale of the graph doesn't allow you to fully appreciate the magnitude of the change here. In 2000, we ate approximately 2.5 ounces, or 280 calories, more processed grains per day than in 1970 (USDA). That has since decreased slightly (34 calories). You might be saying to yourself right now "hey, that plus the 100 calories from sugar adds up to more of an increase than the NHANES data show!" Yes, and I think that points to the fact that the data sets are not directly comparable. NHANES data are self-reported whereas USDA data are collected from vendors. Regardless of the absolute numbers, our processed grain consumption has gone way up since 1970. Wheat is still king. Although we grow a lot of corn in this country, most of it gets fed to animals. We prefer eating wheat without first feeding it to an intermediary. In absolute quantity, wheat consumption has increased more than any other grain (not including corn syrup).
Bye bye whole milk. Hello skim milk (USDA).
This graph represents "added fats", as opposed to fats that occur naturally in meat or milk (the USDA does not track the latter). Added fats include salad oil, cooking oil, deep fry oil, butter, lard, tallow, etc. We are eating a lot more vegetable oil than we were in 1970. It comes chiefly from the industrial, omega-6 rich oils such as soybean, corn and canola. Added animal fats have increased slightly, but it's pretty insignificant in terms of calories.There is an artifact in this graph that I have to point out. In 2000, the USDA changed the way it gathered vegetable oil data. This led to an abrupt, apparent increase in its consumption that is obvious on the graph. So it's difficult to make any quantitative conclusions, but I think it's clear nevertheless that vegetable oil intake has increased considerably.
Between 1970 and 1980, something changed in the U.S. that caused a massive increase in obesity and other health problems. Some combination of factors reached a critical mass that our metabolism could no longer tolerate. The three biggest changes in the American diet since 1970:
- An increase in cereal grain consumption, particularly wheat.
- An increase in sweetener consumption
- The replacement of meat and milk fat with industrial vegetable oils, with total fat intake remaining the same.
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