Apolipoprotein B: a predictor of inflammatory status in postmenopausal overweight and obese women

Abstract

Aims/hypothesis: Inflammation is implicated in the development of type 2 diabetes and CHD, but the trigger of inflammation is unclear. Although in vitro and animal studies support a role of elevated levels of atherosclerotic lipoproteins in the activation of inflammation, plasma cholesterol cannot predict inflammatory markers in humans. Moreover, the association between inflammatory markers and other traditional risk factors of diabetes and CHD is unclear. To increase our knowledge of in vivo regulation of inflammation, we examined the association between several traditional risk factors and inflammatory markers. We hypothesised that because apolipoprotein B (ApoB) reflects atherogenic particle number, it is the primary predictor of inflammatory status. Subjects, materials and methods: We examined the association between several traditional risk factors and plasma high-sensitivity (hs) C-reactive protein (CRP), hsTNF-α, soluble TNF receptor 1, IL-6, orosomucoid, haptoglobin and α 1 -antitrypsin in 77 non-diabetic overweight and obese postmenopausal women. Results: The inflammatory markers correlated positively with total and abdominal adiposity, blood pressure, 2-h OGTT glucose, insulin resistance, triglyceride, total/HDL cholesterol, ApoB, ApoB:apolipoprotein A1 (ApoA1) ratio and Framingham CHD risk points. They correlated negatively with ApoA1, and total, LDL and HDL cholesterol. ApoB was an independent predictor of the interindividual variation in IL-6, hsCRP, orosomucoid, haptoglobin and α 1 -antitrypsin (R 2 range 8-40%); other risk factors were less predictive. Compared with BMI-matched control subjects, women with hyperapobetalipoproteinaemia (hyperapoB) had higher hsTNF-α, IL-6, hsCRP and orosomucoid (increase 17-104%). Conclusions/interpretation: ApoB is the primary predictor of inflammatory markers in postmenopausal overweight and obese women. Given elevated levels of inflammatory markers in hyperapoB women, we hypothesise that hyperapoB women may have an increased risk of developing both CHD and diabetes.

Serum apolipoprotein B predicts dyslipidemia, metabolic syndrome and, in women, hypertension and diabetes, independent of markers of central obesity and inflammation

“…In fact, CRP held in men a modest predictive ability independent of abdominal obesity only regarding dyslipidemia. Based on the finding that apo B was the primary predictor of inflammatory markers in nondiabetic postmenopausal women among a variety of risk parameters including adiposity and IR, 6 the expressed suggestion that high apo B would be associated with elevated risk of developing CHD and diabetes, may be extended further to developing hypertension, dyslipidemia and MS and to men. In the current study, the predictive ability by apo B of combined cardiometabolic disorders might be ascribed to the close relationship of apo B with subclinical inflammation.…”

“…6 It was suggested that high apo B would be associated with elevated risk of developing coronary heart disease ((CHD) and) diabetes. Seeking differences among sexes in the association of apo B and other risk factors with the MS, Dallongeville et al 7 reported that the contribution of apo B to MS was significantly less in women than in men and suggested that different criteria are necessary to define the MS in women and men.…”

Association between physical activity energy expenditure and inflammatory markers in sedentary overweight and obese women

“…This is particularly plausible given our recent publication that showed that the number of apoB100-lipoproteins was the primary predictor of inflammatory markers in overweight and obese postmenopausal women, superior to all lipid levels and independent of adiposity. 28 Moreover, it is well accepted that larger LDL particles are less proinflammatory than smaller denser LDL particles. 43,44 Energy expenditure may be associated with leptin, 45,46 which is associated with inflammatory markers.…”

“…The postmenopausal women were included in the two studies if they (1) were overweight or obese with body mass index (BMI) X27 kg m À2 , 28 (2) aged between 46 and 70 years, (3) had biological confirmation of the menopause status (cessation of menstruation for more than 1 year and plasma follicle-stimulating hormone X30 U l À1 ), (4) were not taking hormone replacement therapy, (5) were non-smokers, and (6) were sedentary with o2 h per week of structured exercise. On physical examination and biological testing, all participants had no (1) diabetes (fasting glucose 47.1 mmol l À1 or 2-h plasma glucose of 411.1 mmol l À1 after a 75 g OGTT), (2) uncontrolled thyroid disease, cardiovascular or peripheral vascular disease, (3) use of hormone replacement therapy, estrogen, narcoleptics, steroids, lipid-lowering and antihypertensive agents, (4) dyslipidemia or hypertension requiring immediate medical intervention (total cholesterol 48 mmol l À1 , triglyceride 44.5 mmol l À1 , blood pressure 4160/100 mm Hg, (5) history of alcohol or drug abuse, (6) abnormal blood laboratory values (creatinine 4135 mmol l À1 ), (7) use of drugs or medications to stimulate weight loss, psychoactive drugs and adrenergic agonists by any route, (8) body weight fluctuation in the last 3 months (9) known history of inflammatory disease as well as cancer.…”

“…BMI was calculated as body weight (kg)/ height (m) 2 . 28 Visceral adipose tissue (VAT) and subcutaneous adipose tissue were assessed by computed tomography scan (General Electric Medical Systems, Milwaukee, WI, USA) at the L4-L5 vertebral disk as previously described. 29 Resting energy expenditure REE was measured after a 12-h fast by indirect calorimetry, as previously described.…”