Regulation of Lipoprotein Metabolism in Obese Men

The University of Western Australia48 enrolled

Overview

Visceral obesity is strongly associated with dyslipidaemia (hypertriglyceridaemia, low HDL-cholesterol and mildly elevated LDL-cholesterol) and insulin resistance, key characteristics of metabolic syndrome (MetS). Recent evidence has clearly established that the risk of CVD is increased in subjects with the MetS. The precise reason for this remains unclear, but appears to be closely related with dyslipidaemia. Effective management of dyslipidaemia is important to reduce the risk of CVD in these subjects. Hypothesis: Inhibition of hepatic cholesterol synthesis by statins and triglyceride synthesis by fish oils improve lipoprotein metabolism in visceral obese men.

The study employed a factorial study design, stable isotopy and mathematical modelling to examine the independent and combined effects of decreasing cholesterol substrate availability with atorvastatin and decreasing triglyceride substrate availability with fish oils on lipoprotien kinetics (apoB, apoA, apoC-III and chylomicron remnants) in insulin-resistant men with visceral obesity.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Obesity Dyslipidemia Insulin Resistance

Eligibility

Sex: MALEMin age: 20 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Obesity was defined as a waist circumference \>100 cm, waist:hip ratio \>0.97 and BMI \>29 kg/m2. * Subjects were selected for having insulin-resistance, defined as a homostasis model assessment (HOMA) score (21) \>5.1 (i.e. one SD above the mean for a reference population of 22 lean, normolipidemic healthy males of similar age). * All subjects had plasma triglyceride \>1.2 mmol/L and cholesterol \>5.2 mmol/L at screening while consuming ad libitum, weight-maintaining diets Exclusion Criteria: * diabetes mellitus, apolipoprotein E2/E2 genotype, macroproteinuria, creatinemia, hypothyrodism, or abnormal liver enzymes. * Subjects did not consume fish oil supplements or drank more than 30g alcohol/day. * None reported a history of CVD, or was taking medication or other agents known to affect lipid metabolism.

Outcomes

Primary Outcomes

Fractional catabolic rate of apoB, apoA, apoC-III and chylomicron remnants (before and after 6 week treatments)

Production rate of apoB, apoA, apoC-III and chylomicron remnants (before and after 6 week treatments)

Secondary Outcomes

Cholesterol

Triglyceride

LDL-cholesterol

Adipocytokines

Genetic polymorphisms