Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated b...Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index(BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome(MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods(fat). However, high-carbohydrate rich(CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering highdensity lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.展开更多
Obesity increases the risk for type 2 diabetes through induction of insulin resistance.Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been sev...Obesity increases the risk for type 2 diabetes through induction of insulin resistance.Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance.In those hypotheses,inflammation,mitochondrial dysfunction,hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention.Oxidative stress,endoplasmic reticulum(ER)stress,genetic background,aging,fatty liver,hypoxia and lipodystrophy are active subjects in the study of these concepts.However,none of those concepts or views has led to an effective therapy for type 2 diabetes.The reason is that there has been no consensus for a unifying mechanism of insulin resistance.In this review article,literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance,in which insulin resistance is a result of energy surplus in cells.The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase(AMPK)signaling pathway.Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance.In support,many of existing insulin sensitizing medicines inhibit ATP production in mitochondria.The effective therapies such as weight loss,exercise,and caloric restriction all reduce ATP in insulin sensitive cells.This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity,which may apply to insulin resistance in aging and lipodystrophy.展开更多
Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased f...Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin's role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.展开更多
文摘Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index(BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome(MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods(fat). However, high-carbohydrate rich(CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering highdensity lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.
基金Jianping Ye is supported by the National Institute of Health research projects(DK085495,DK068036).
文摘Obesity increases the risk for type 2 diabetes through induction of insulin resistance.Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance.In those hypotheses,inflammation,mitochondrial dysfunction,hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention.Oxidative stress,endoplasmic reticulum(ER)stress,genetic background,aging,fatty liver,hypoxia and lipodystrophy are active subjects in the study of these concepts.However,none of those concepts or views has led to an effective therapy for type 2 diabetes.The reason is that there has been no consensus for a unifying mechanism of insulin resistance.In this review article,literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance,in which insulin resistance is a result of energy surplus in cells.The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase(AMPK)signaling pathway.Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance.In support,many of existing insulin sensitizing medicines inhibit ATP production in mitochondria.The effective therapies such as weight loss,exercise,and caloric restriction all reduce ATP in insulin sensitive cells.This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity,which may apply to insulin resistance in aging and lipodystrophy.
基金the National Heart,Lung and Blood Institute,Nos.PO1HL-051971 and R00HL112952the National Institute of General Medical Sciences,No.P20GM-104357the American Heart Association,No.14SDG20490339
文摘Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin's role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.
