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Abstract. Pre␤1-HDL is a minor HDL subfraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37°C incubation, plasma pre␤1-HDL decreases over time due to its conversion to ␣-migrating HDL by lecithin: cholesterol acyltransferase (LCAT). This conversion may be delayed in hemodialysis patients who have decreased LCAT activity. To clarify whether LCAT-dependent conversion of pre␤1-HDL to ␣-migrating HDL is delayed in hemodialysis patients, pre␤1-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37°C incubation with and without the LCAT inhibitor. It was found that the baseline pre␤1-HDL concentration in hemodialysis patients was more than twice that in the controls (44.9 Ϯ 21.4 versus 19.8 Ϯ 6.7 mg/L apoAI; P Ͻ 0.001). After 2-h incubation, the LCAT-dependent decrease in pre␤1-HDL in hemodialysis patients was about one-third of that in the controls (30 Ϯ 27 versus 97 Ϯ 17% of baseline; P Ͻ 0.01). The LCAT-dependent rate of decrease in pre␤1-HDL levels (DR pre␤1 ) was the same for samples from hemodialysis patients exhibiting normal (Ն1.03 mmol/L) and low HDLcholesterol levels (32 Ϯ 32 versus 28 Ϯ 23% of baseline; NS). DR pre␤1 was positively correlated with LCAT activity (r ϭ 0.617; P Ͻ 0.001). In conclusion, the LCAT-dependent conversion of pre␤1-HDL to ␣-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of pre␤1-HDL may accelerate atherosclerosis in hemodialysis patients.

Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFβ signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity.

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We have established an immunoassay for pre ␤ 1-HDL (the initial acceptor of cellular cholesterol) using a monoclonal antibody, MAb55201. Because pre ␤ 1-HDL is unstable during storage, fresh plasma must be used for pre ␤ 1-HDL measurements. In this study, we describe a method of stabilizing pre ␤ 1-HDL, and evaluate the analytical performance of the immunoassay for pre ␤ 1-HDL. Fresh plasma was stored under various conditions with or without a pretreatment consisting of a 21-fold dilution into 50% (v/v) sucrose. Pre ␤ 1-HDL concentration was measured by immunoassay. In nonpretreated samples, pre ␤ 1-HDL decreased significantly from the baseline after 6 h at room temperature. Although pre ␤ 1-HDL was more stable at 0 ؇ C than at room temperature, it increased from 30.2 ؎ 8.5 (SE) to 56.5 ؎ 5.5 mg/l apolipoprotein A-I (apoA-I) ( P Ͻ 0.001) in hyperlipidemics, and from 18.4 ؎ 1.2 to 37.9 ؎ 3.3 mg/l apoA-I ( P Ͻ 0.001) in normolipidemics after 5-day storage. After 30-day storage at ؊ 80 ؇ C, pre ␤ 1-HDL increased from 29.0 ؎ 4.0 to 38.0 ؎ 5.7 mg/l apoA-I ( P Ͻ 0.001) in hyperlipidemics, whereas it did not change in normolipidemics. In pretreated samples, pre ␤ 1-HDL concentration did not change significantly under any of the above conditions. Moreover, pre ␤ 1-HDL concentrations determined by immunoassay correlated with those determined by native two-dimensional gel electrophoresis (n ‫؍‬ 24, r ‫؍‬ 0.833, P Ͻ 0.05).An immunoassay using MAb55201 with pretreated plasma is useful for clinical measurement of pre ␤ 1-HDL.