Obesity, Cholesterol And Dyslipidemia

Clinician's Perspective:

• Dyslipidemia is an imbalance of lipids in the bloodstream, characterized by high LDL cholesterol, low HDL cholesterol, or high triglycerides. Dyslipidemia increases the risk of developing cardiovascular disease.

• 60% to 70% of individuals with obesity have dyslipidemia (abnormal blood lipid levels).

• For every 1kg of weight lost through lifestyle changes, there is a corresponding 1.33 mg/dL decrease in Triglycerides.

• Medications like Tirzepatide have demonstrated the ability to reduce Triglycerides by up to 40% amongst patients who have lost more than 30% body weight.

• Roux-en-Y Gastric Bypass (a type of bariatric surgery) achieves a dyslipidemia remission rate of 60.4%.

What is Dyslipidemia?

Dyslipidemia is an imbalance of lipids in the bloodstream, characterized by unhealthy levels of LDL cholesterol, HDL cholesterol, or triglycerides. It leads to increased risk of developing heart disease, stroke and peripheral vascular disease.

Obesity may lead to dyslipidemia. This is characterized by:

• High​Triglycerides (blood fats)
• Low HDL-C (high-density lipoprotein cholesterol, often called "good" cholesterol)
• High LDL-C (low-density lipoprotein cholesterol, often called "bad" cholesterol).

LDL-C is the most important factor. High levels of LDL-C increases cardiovascular disease risk.

It is important to know that a normal level of LDL-C on standard lipid panel testing can be deceptive since it does not directly measure the actual number of LDL particles. Many patients have a "normal" LDL-C score but may actually have abnormally high number of small, dense LDL particles. To see the true risk level, we have to measure "apoB". Since every single LDL particle has exactly one apoB protein attached to it, measuring apoB acts like a "headcount" that reveals the real volume of LDL-C.

LDL-C Clogs Up Our Blood Vessels

Having high levels of small LDL-C particles is especially dangerous. These particles are much more dangerous because they are "stealthy" and "sticky." Their tiny size allows them to slip through the lining of your artery walls much easier than normal-sized particles. Once they get inside, they act like Velcro, binding to structural proteins called "proteoglycans" that trap them in the artery wall. Because they stay in your system longer and get stuck so easily, they quickly turn into the "plaque" that causes heart attacks and strokes.

Liver Health Is The Key

In obesity, the liver becomes a "fat-processing factory" that is overwhelmed by a constant flood of fatty acids.

These fatty acids come from three main sources: visceral fat, de novo lipogenesis (the liver's creation of new fat from sugar), and our diet.

To cope, the liver pumps out an excessive number of VLDL (Very Low Density Lipoprotein), which are like large trucks designed to carry fats through the blood. When this happens, it will show up on the lipid panel blood test as high triglycerides.

Normally, VLDL drop off their fat and are quickly cleared away by the liver. However, in obesity, the liver overproduces Apo C-III (a protein that inhibits the clearance of fats from the blood). Apo C-III delays the breakdown of VLDL particles. As a result, these particles remain in the blood stream, eventually shrink into dangerous, small dense LDL particles.

Lifestyle and Diet

What we eat will affect our lipid profile. Studies show that low-carbohydrate diets are more effective at reducing triglycerides and raising HDL-C than low-fat diets. Conversely, low-fat diets remain superior for lowering LDL-C.

It is important to note that in some individuals, particularly those who are lean or using ketogenic (very low carb) diets to manage weight, LDL-C levels can spike to extreme levels—while triglycerides remain very low (under 70 mg/dL). This may lead to increased cardiovascular risk.

Pharmacotherapy

Statins and Ezetimibe are effective treatments for dyslipidemia.

The advent of GLP-1 and GIP receptor agonists has shifted the treatment landscape, allowing doctors to treat obesity and dyslipidemia at the same time. In the STEP and SURMOUNT trials, medications like Semaglutide and Tirzepatide induced lipid improvements that were directly proportional to weight loss. For instance, Tirzepatide users losing more than 30% of their body weight saw their triglycerides drop by approximately 40%.

Bariatric Surgery

For those with severe obesity, metabolic bariatric surgery (weight loss surgery) remains the most potent tool for lipid correction. Beyond simple weight loss, procedures like Roux-en-Y Gastric Bypass (RYGB) induce hormonal changes and nutrient malabsorption that lead to higher rates of lipid remission compared to Sleeve Gastrectomy (a procedure that removes a large portion of the stomach).

Evidence Strength: This comprehensive review is supported by high-quality evidence from multiple large-scale Randomized Controlled Trials (RCTs) and meta-analyses, providing definitive data on the metabolic and therapeutic aspects of dyslipidemia. Final Rating: ★★★★★

Source: Read the full study