Effects of acidosis on leptin secretion from 3T3-L1 adipocytes and on serum leptin in the uraemic rat

Abstract

Marked hyperleptinaemia and metabolic acidosis are common findings in patients with chronic renal failure. In animal models, both leptin administration and acidosis reduce food intake. However, leptin causes loss of body fat, while acidosis induces muscle wasting. Whether a low pH and leptin production are related has not been studied. Leptin secretion was measured in cultured 3T3-L1 adipocytes exposed to acid or control pH for up to 96 h. In addition, serum leptin was compared between acidotic and bicarbonate-treated uraemic Wistar rats using the remnant model. Leptin levels in the culture medium were decreased at an acid pH of 7.1 compared with a control pH of 7.5 at 96 h (562+/-78 and 831+/-103 pg.48 h(-1). well(-1) respectively; mean+/-S.E.M.; P=0.037). Similarly, serum leptin in uraemic rats was found to be lower in the acidotic group than in the bicarbonate-treated group, although this observation fell just short of statistical significance (1273+/-171 compared with 2059+/-376 pg/ml; P=0.07). In conclusion, acidosis decreases leptin secretion from cultured adipocytes. Accordingly, acidotic uraemic rats seem to exhibit lower serum leptin levels than their bicarbonate-supplemented counterparts. This study is the first report providing a link between acidosis and leptin levels.

Leptin and hypertension in non-obese patients in renal replacement therapy

“…Metabolic acidosis has been shown to decrease serum leptin in uremic rats through suppression of leptin secretion from adipocytes [27], in agreement with our finding. In contrast, other previous studies reported that blood hydrogen ion concentration does not influence substantially or only moderately leptin serum concentrations, or the correction of metabolic acidosis in dialysis patients can decrease leptin [28,29].…”

Acidosis Downregulates Leptin Production from Cultured Adipocytes through a Glucose Transport-Dependent Post-transcriptional Mechanism

“…A low pH of 7.1 was associated with a significantly reduced leptin output both at 48 and 96 h, confirming our previous report (9) (Figure 1). In contrast, leptin mRNA was not affected by low pH at 48 h ( Figure 2).…”

“…In contrast, circulating leptin acutely decreases after fasting or calorie restriction in both rodents and humans (7,8). Like starvation, metabolic acidosis is associated with lower serum leptin in uremic rats (9). However, the mechanism or mechanisms that link acidosis and leptin is unknown.…”

“…Total DNA, protein, and triglycerides were extracted from the cells exactly as described previously (9). For leptin mRNA experiments, the cells were treated similarly, after which 1.5 ml Trizol was added.…”

“…Leptin concentrations in cell culture media were determined using a sandwich ELISA for mouse leptin (Quantikine M; R&D Systems) as described previously (9).…”