Complications of Visceral Obesity

Obesity increases the risk of chronic complications. There is also compelling evidence that a high-risk form of overweight/obesity—visceral obesity—is linked to the most severe metabolic abnormalities. With its peculiar metabolism, hyperlipolytic activity, and anatomic location, excess visceral fat plays a key role in insulin resistance, especially in the liver. This can cause glucose intolerance and type 2 diabetes in genetically susceptible individuals. High amounts of visceral fat are also closely tied to the typical atherogenic dyslipidemia found in individuals with abdominal obesity. High blood pressure, a pro-thrombotic state, and—more recently—a pro-inflammatory profile are other abnormalities seen mainly in individuals with excess visceral fat, irrespective of body weight. In addition to its possible role in causing insulin resistance and related metabolic abnormalities, excess visceral fat may also be a marker of ectopic fat deposition. This means that visceral obesity may indicate that an obese individual has too much fat at undesirable locations—such as the liver, skeletal muscle, and the pancreas—which can cause serious problems with carbohydrate and lipid metabolism.

Key Points

• Chylomicrons (dietary) and VLDL (endogenous) are the main triglyceride carriers in the blood. LDL and HDL are the main cholesterol carriers.
• LDL delivers cholesterol to peripheral tissues. HDL delivers cholesterol from tissues to the liver.
• The “traditional” dyslipidemia typically associated with visceral obesity includes hypertriglyceridemia, the presence of small, dense LDL, and low HDL cholesterol levels. All three abnormalities are metabolically linked.
• Chylomicron and VLDL remnants (not routinely measured) are also elevated in visceral obesity.
• Under pro-atherogenic conditions, chylomicron remnants, VLDL remnants, and small LDL deliver cholesterol to the artery wall (pro-atherogenic). HDL removes cholesterol from the artery wall (anti-atherogenic).
• Insulin resistance plays a key role in linking visceral obesity and dyslipidemia.
• A newer set of metabolic risk factors—the “atherogenic metabolic triad”—includes hyperinsulinemia, hyperapo B, and small LDL particles.
• These risk factors enable additional subjects at risk of CVD to be identified.
• A number of drugs are available to treat each component of the dyslipidemia of visceral obesity. But a key therapeutic objective remains the reduction of visceral fat, the primary cause of dyslipidemia.

Read more on Atherogenic Dyslipidemia.

Key Points

• Glucose is abundant in a wide range of foods. In the fasted state, the liver provides the bulk of glucose to the bloodstream through glycogenolysis and gluconeogenesis.
• Insulin optimizes glucose uptake by skeletal muscle, its major peripheral user. Insulin also reduces liver glucose production after a meal and reduces fatty acid release by adipose tissue. These three major functions are important for glucose homeostasis.
• Expansion of visceral fat causes adipocyte hypertrophy. This process triggers macrophages that, together with the enlarged adipocytes, locally secrete insulin-resistance-promoting molecules.
• Hypertrophied insulin-resistant visceral adipocytes release more fatty acids and proinflammatory adipokines into the bloodstream. The portal circulation carries these to the liver where they promote steatosis, insulin resistance, and local inflammation. The systemic circulation carries fatty acids and proinflammatory molecules to skeletal muscle where they promote lipid accumulation, insulin resistance, and local inflammation.
• Insulin resistance also affects the function of other systems and organs, including endothelial cells and cells of the vascular wall. This further increases CVD risk.
• Insulin resistance is believed to play a role in the development of many metabolic abnormalities that define the metabolic syndrome. It is also believed to be a strong link between visceral obesity and increased risk of type 2 diabetes and CVD.
• Targeting the fundamental cause of obesity-related insulin resistance by reducing visceral fat mass remains an important therapeutic objective.

Read more on Glucose/Insulin Homeostasis.

Key Points

• Adipose tissue is more than an organ that mobilizes energy stored in the form of triglycerides. It is also an endocrine organ that secretes adipokines, which are involved in the atherogenic/diabetogenic metabolic risk profile of abdominal obesity.
• Obesity, especially visceral obesity, is associated with chronic low-grade inflammation.
• This inflammation may lead to insulin resistance and other features of the metabolic syndrome associated with visceral obesity, such as dyslipidemia.
• The inflammatory component of CHD has been emphasized in recent years and may increase risk of acute coronary syndrome. However, hs-CRP may be a marker rather than a cause of metabolic disturbances that increase CVD risk.

Read more on Inflammation.

Key Points

• Obese, insulin-resistant subjects and type 2 diabetic patients often have a pro-thrombotic state.
• Atherothrombotic complications of the metabolic syndrome are partly due to a dysregulation of hemostasis. This induces a pro-thrombotic state that includes endothelial activation, platelet hyperactivity, hypercoagulability, and hypofibrinolysis.
• Hypofibrinolysis because of elevated PAI-1 levels is a core feature of the metabolic syndrome.
• Weight loss improves all pro-thrombotic factors, indicating that obesity is a modifiable risk factor for thrombosis.

Read more on Pro-Thrombotic State.

Key Points

• Hypertension is a well-known, potent, and modifiable CVD risk factor.
• Hypertension-related CVD risk escalates when other risk factors are present.
• Visceral obesity and hypertension are linked.
• The amount of visceral fat may explain the association between obesity, fasting insulin, insulin sensitivity, and blood pressure.

Read more on Hypertension.