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.

Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

“…In this study, leptin remained unaltered despite pronounced metabolic and hormonal perturbations (NEFAs, glycerol, glucose, and cortisol increases) independent of intensity. Although increased glucose uptake by peripheral tissues in the presence of lactic acidosis may decrease blood leptin (12), the increase in blood lactate (four- to ninefold) in the present study (indicative of increased glucose uptake) was not accompanied by a leptin decline. It is possible that these protocols did not induce adequate glucose uptake and utilization capable of reducing serum leptin.…”

Interrelationship between plasma leptin concentration and severity of metabolic acidosis in haemodialysed patients with chronical renal failure

“…The concerted interaction of these factors may explain, why no strong associations were found in our study between blood hydrogen ion concen-tration and leptinemia in uraemic patients. Only in vitro, adipocytes 3T3-L1 cultured in acidic medium at pH 7.1 showed a significantly decreased leptin secretion after 96 hours (Teta et al, 1999). It should be stressed that, these cells were not exposed to uraemic toxins.…”

“…Hyperleptinaemia per se shows a negative feedback effect on leptin secretion by adipocytes. Among other factors suppressing leptin secretion uraemic toxins (PTH, AGEs and other) (Kokot et al, 1999; not published data by Kokot et al), hyperinsulinaemia (Steinvinkel et al, 1997) and acidosis (Teta et al, 1999) are to be mentioned. The concerted interaction of these factors may explain, why no strong associations were found in our study between blood hydrogen ion concen-tration and leptinemia in uraemic patients.…”

“…It has been reported, that in vitro mouse adipocytes exposed to acidotic medium (pH 7.1) secrete less leptin (Teta et al, 1999). In addition serum leptin level in uraemic rats treated with bicarbonate tended to be higher than in animals not supplemented with bicarbonate (Teta et al, 1999). The impact of uraemic acidosis on leptinaemia in humans was not studied until now.…”

“…Unfortunately in this metabolic setting it is difficult to assess the individual contribution of metabolic acidosis, hypoinsulinaemia and sympathetic nervous system overactivity on leptinaemia. As well known all these factors may influence significantly plasma leptin concentration (Teta et al, 1999;Hathout et al, 1999;Pinkey et al, 1998).…”