Plasma and gonadal fat pads were isolated after an overnight fast from 10-week-old wild-type mice (B100/B48) and mice lacking apoB100 (B48) or expressing only apoB100 (B100). (A) Western blots of plasma performed with rabbit anti-mouse apoB antibodies. (B) Gonadal fat pad cell volume (n≥12 mice per group (B100/B48;B48; B100); p = 0.99; DF = 2,35; F-value = 0.015). (C) Basal (p = 0.13; DF = 2,39; F-value = 2.4), noradrenaline-stimulated (p = 0.019; DF = 2,36; F-value = 3.8), and 8-bromo cyclic AMP–stimulated lipolysis (p = 0.02; DF = 2,38; F-value = 3.8) (n≥12 mice per group). (D) Resting oxygen consumption (VO₂) and respiratory quotient (RQ) in mice kept at different environmental temperatures (n = 7–8 mice mice per group; DF = 1,13) p = 0.01; F-value = 3.3 for VO₂ and p = 0.015; F-value = 3.1 for RQ). Error bars in (B–D) indicate SD. p-values were determined by ANOVA.

In the normal state there is a balance between production of hepatic apoB100 containing lipoproteins and release of free fatty acid (FFA) from the adipose tissue. In FCHL patients, who have lower noradrenaline-induced lipolysis and increased levels of plasma lipoproteins containing aoB100, lowered lipid synthesis and decreased adipocyte fatty acid trapping lead to elevated levels of FFA in the circulation. Increased levels of circulating FFA activate apoB100 synthesis leading to elevated plasma apoB100 containing lipoprotein levels. In this fashion an imbalance between liver-adipose tissue is created and a “vicious circle” evolves. HSL indicates hormone sensitive lipase.

(A) Linear regression plot of fat cell lipolysis (glycerol release) and plasma apoB100 levels in 48 overweight but healthy men. The linear regression r-value = −0.5, p<0.001. (B) Basal (n = 9; p = 0.94; DF = 2,24; F-value = 0.065) and (C) noradrenaline-stimulated (noradrenaline/basal) (n = 9; p<0.05; DF = 2,24; F-value = 3.6) lipolysis in human differentiated pre-adipocytes incubated with equal concentrations (40 µg apoB100/ml medium) of human VLDL or LDL or with vehicle alone for 48 hours. (D) Inhibition of lipolysis in human differentiated pre-adipocytes incubated without or with human LDL at five concentrations (20, 30, 40, 60, 80 µg apoB100/ml medium) for 48 hours (n = 3 for each concentration; p = 0.001; DF = 2,5,10; F-value = 10.4) and (E) with different incubation times (8, 24 and 48 hours) with 40 µg apoB100/ml medium (n = 5 for each time point; DF = 2,12) p = 0.61; F-value = 0.48 for vehicle and p = 0.007; F-value = 7.6 for apoB100 incubation. (F) Noradrenaline-stimulated (noradrenaline/basal) lipolysis in human differentiated pre-adipocytes incubated with vehicle alone, native LDL and two forms of reconstituted LDL (40 µg apoB100/ml medium) for 48 hours (n = 29–34 in each group). “Trilinoleate” indicates reconstituted LDL in which cholesterol esters had been replaced with Trilinoleate. “Chol. linoleate” indicates reconstituted LDL in which cholesterol esters had been replaced with cholesteryl linoleate. (G) mRNA expression (n = 4–8) in human differentiated pre-adipocytes incubated with human LDL (40 µg apoB100/ml medium) presented as % of control cells (not exposed to LDL). Error bars in (B,C,G) indicate SD and in (D,E,F) indicate SE. p-values for (B, C, D, E) were determined by ANOVA and for (F,G) un paired t-test. *p<0.05, **p<0.01, ***p<0.001 indicate Fisher's Post-hoc test.

(A) Basal and noradrenaline-stimulated lipolysis in 3T3-L1 cells incubated with equal numbers of mouse lipoproteins containing only apoB100 (40 µg/ml medium, n = 10) or apoB48 (20 µg/ml medium, n = 4) or with vehicle alone (n = 7) for 48 hours; DF = 2,18 (p = 0.79; F-value = 0.24 for basal and p<0.001; F-value = 10.4 for noradrenaline-stimulated lipolysis). (B) Percent inhibition of lipolysis mediated by incubation of 3T3-L1 cells with mouse lipoproteins containing apoB100 at high (80 µg apoB/ml medium) and low (40 µg apoB/ml medium) concentrations or with vehicle alone (Control) (n = 9 for each concentration; p = 0.013; DF = 2,24; F-value = 5.6) for 48 hours. (C) Fat cell volume in gonadal fat pads isolated from Ldlr^−/−Apob^100/100 mice (Ldlr^−/−, n = 13) and Ldlr^+/+Apob^100/100 mice (Ldlr^+/+, n = 17) mice (p = 0.23). (D) Basal (p<0.05) and noradrenaline-stimulated (p<0.01) lipolysis in the mice described in (C). Error bars indicate SD. p-values were determined by ANOVA in (A–B) and unpaired t-test in (C–D), *p<0.05, **p<0.01 (t-test).