Decreased Plasma Leptin Levels Research Articles

Downregulation of leptin by free fatty acids in rat adipocytes: Effects of triacsin C, palmitate, and 2-bromopalmitate

Free fatty acid (FFA) has been reported to decrease leptin mRNA levels in 3T3-L1 adipocytes. When using this cell line, it is difficult to determine the protein levels because a very small amount of leptin is secreted into the medium. The effect of FFA on leptin secretion from adipocytes has not yet been determined. In addition, in vivo studies have failed to demonstrate a FFA-induced decrease in plasma leptin levels. To clarify the effect of FFA on leptin production, we investigated the leptin protein level in the medium and the mRNA level in primary cultured rat adipocytes treated with triacsin C, which is a potent inhibitor of acyl-coenzyme A (CoA) synthetase, palmitate, and 2-bromopalmitate. Triacsin C (0 to 5 x 10(-5) mol/L) decreased leptin concentrations in the culture medium in a dose-dependent manner. Leptin mRNA levels were decreased to 10% of the control in the presence of triacsin C. The concentration of triacsin C needed to suppress leptin production was similar to the Ki value (approximately 10(-5) mol/L) for inhibition of acyl-CoA synthetase. Both palmitate and 2-bromopalmitate decreased leptin concentra-tions but did not affect the triacsin C-induced decrease in leptin additively. In conclusion, both protein and mRNA levels of leptin were decreased by triacsin C and FFA in primary cultured rat adipocytes. Our findings suggest that FFA is involved in the regulation of leptin production in adipocytes.

Metabolic control of food intake and estrous cycles in syrian hamsters. I. Plasma insulin and leptin.

The "adipostat hypothesis" refers to the idea that circulating hormone concentrations reflect levels of body adiposity and act as signals to control food intake and reproduction. Implicit in the adipostatic hypothesis are the following two assumptions: 1) plasma levels of adipostatic hormones accurately reflect body fat content and 2) decreased plasma concentrations of adipostatic hormones necessarily result in increased food intake and inhibited reproductive processes. The present experiments are designed to test these assumptions. Fat and lean Syrian hamsters were either fasted for 12, 24, 36, or 48 h or allowed ad libitum access to food. Contrary to the first assumption, plasma leptin and insulin levels in fat hamsters dropped dramatically by 12 h after the start of a fast, with no significant change in body fat content and no postfast hyperphagia. Lean hamsters showed anestrus after a 48-h fast but not after a 24-h fast. Contrary to the second assumption of the lipostatic hypothesis, lean hamsters fasted for 24 h and then refed for the next 24 h had leptin levels that were not significantly elevated compared with those of 48-h-fasted hamsters. Thus, in adult female Syrian hamsters, plasma leptin concentrations do not accurately reflect body fat content under all conditions; normal estrous cyclicity does not necessarily require plasma leptin concentrations higher than those of fasted hamsters; and decreased plasma leptin levels do not result in increased food intake.

Decreased plasma leptin levels in lean and obese Zucker rats after treatment with the serotonin reuptake inhibitor fluoxetine.

Leptin inhibits feeding, stimulates thermogenesis and decreases body weight. Serotonin reduces food intake when injected into the hypothalamus and may interact with other neurotransmitters in the control of appetite. We therefore investigated the effects of the serotonergic drug fluoxetine, which inhibits serotonin reuptake, on food intake and plasma leptin levels in lean and obese Zucker rats. Fluoxetine significantly reduced food intake in lean and obese rats, both acutely after a single injection (10 mg/kg) and during continuous subcutaneous infusion (10 mg/kg/day for 7 days). Plasma leptin levels were reduced after both 4 hours and 7 days of fluoxetine administration in lean and after 7 days in fatty rats (all p<0.01). We have previously suggested that serotonin may decrease food intake by inhibiting neuropeptide Y neurones, and we further suggest that it also inhibits leptin, possibly by an effect on white adipose tissue.

Effects of mild aerobic exercise and a mild hypocaloric diet on plasma leptin in sedentary women.

1. The present study was conducted to investigate whether mild aerobic exercise and a mild hypocaloric diet, instead of severe restrictions on caloric intake, would affect weight reduction and plasma leptin concentrations. 2. Forty-one middle-aged sedentary women (15 obese and 26 non-obese) participated in a 12 week lifestyle-modification programme to reduce cardiovascular risk factors. Bodyweight, body composition, plasma leptin concentrations, serum lipid profiles, fasting plasma glucose and fasting plasma insulin were measured before and after the 12 week intervention. The intervention consisted of aerobic exercise, corresponding to approximately 50% of maximal oxygen consumption, and personal diet counselling. 3. Bodyweight decreased by (mean +/- SD) 3.9 +/- 3.4 kg in the obese group (P < 0.05) and by 1.7 +/- 1.8 kg in the non-obese group (P < 0.05). The plasma leptin concentration decreased significantly from 14.7 +/- 5.3 to 8.9 +/- 3.6 ng/mL in the obese group (P < 0.001) and from 7.6 +/- 3.9 to 5.6 +/- 2.2 ng/mL in the non-obese group (P < 0.01). 4. Overall, for all subjects, both pre- and postintervention, the plasma leptin concentration was significantly correlated with body mass index (BMI; pre-intervention: r = 0.73, P < 0.0001; postintervention: r = 0.67, P < 0.0001), fat mass (FM; pre-intervention: r = 0.74, P < 0.0001; postintervention: r = 0.63, P < 0.0001) and fasting plasma insulin (pre-intervention: r = 0.66, P < 0.001; postintervention: r = 0.45, P < 0.01). The change in plasma leptin concentration was significantly correlated with the respective changes in BMI (r = 0.64, P < 0.0001), FM (r = 0.48, P < 0.01) and fasting plasma insulin (r = 0.58, P < 0.0001). Interestingly, the ratio of plasma leptin concentration to BMI or FM diminished significantly after intervention. In addition, we found that the plasma leptin concentration decreased in participants whose FM did not decrease. These results suggest that the production of leptin per unit FM decreased after intervention. 5. Mild aerobic exercise and a mild hypocaloric intake decreased body mass and the plasma leptin level in Japanese middle-aged sedentary women. This decrease in plasma leptin levels was likely to be associated with weight reduction plus some unknown factor(s).

Recombinant human insulin-like growth factor-I (IGF-I) therapy decreases plasma leptin concentration in patients with chronic renal insufficiency.

To determine the relationship between plasma leptin and insulin-like growth factor-I (IGF-I) levels in healthy subjects and patients with chronic renal insufficiency at baseline, and during administration of recombinant human IGF-I in the renal impaired patients. 20 healthy subjects (six men, 14 women, age: 42.7 +/- 3.2 y) and nine subjects with chronic renal insufficiency (five men, four women, age: 53.6 +/- 3.7 y). Daily s.c. injection of recombinant human IGF-I (50 micrograms/kg) for 24 d. Fasting plasma levels of leptin, IGF-I, growth hormone, C-peptide, glucagon and IGF binding proteins by specific radioimmunoassays at baseline in all subjects and serially during IGF-I therapy in the renal impaired subjects. Baseline leptin levels were correlated with body mass index (BMI, R = 0.72, P = 0.0001) but not IGF-I levels (R = 0.02). During IGF-I therapy, plasma IGF-I levels increased from 128 +/- 17.4 ng/ml at baseline to 250 +/- 36.8 ng/ml on day 3 (P = 0.003) and 323 +/- 61.6 ng/ml on day 24 (P = 0.01), whereas leptin levels declined: 24.4 +/- 10.3 ng/ml (baseline), 19.5 +/- 6.2 ng/ml (day 3, P = 0.028), and 17.2 +/- 4.9 ng/ml (day 24, P = 0.05). Basal plasma leptin and IGF-I levels are not correlated; however, chronic administration of recombinant IGF-I is associated with an early and sustained decrease in plasma leptin levels. IGF-I may have an inhibitory effect on leptin secretion in humans.

The effect of exercise training on leptin levels in obese males.

The effect of endurance training on plasma leptin levels was investigated in 15 obese male subjects (age 37.3 +/- 5.2 yr, body weight 96.5 +/- 13.6 kg, and body mass index 29.8 +/- 3.0 kg/m2) in a weight loss and exercise program. After 4 mo of treatment consisting of a very low energy diet (VLED) and endurance exercise training (3-4 times weekly, 1 h sessions, moderate intensity), two groups were formed. One group continued the exercise sessions (trained subjects, n = 7) and the other group stopped with the exercise program (control, n = 8). Measurements of anthropometry, aerobic power, and fasted blood samples were executed at fixed time points (0, 2, 4, 10, and 16 mo). With partial regression analysis, keeping the changes in insulin and body fat percentage constant, it was shown that the number of hours of exercise training was significantly correlated with changes in leptin levels, during the 16-mo period (r = 0.56, P < 0.05). Changes in insulin levels were significantly related to the changes in leptin levels (r = 0.47, P < 0.05), which were less for changes in body fat percentage (r = 0.42, P = 0.07). During the VLED, the change in insulin concentration affected leptin levels significantly (r = 0.79) but changes in body fat percentage were not noted. It is concluded that endurance exercise training decreased plasma leptin levels independently of changes in plasma insulin levels and body fat percentage.