The Effects of Gender, Fat Mass Distribution, and Weight Loss on Free Leptin Index

Abstract

Leptin (LEP) is an adipokine that is associated with appetite regulation and metabolism and its concentration in obese adults is in proportion to total adipose tissue, suggestive of a state of LEP resistance. LEP acts on the hypothalamus inhibiting appetite and is associated with additional metabolic activities. LEP circulates as both a free and active polypeptide and in an inactive complex with the soluble leptin receptor (LRe), the ratio of the two is the free leptin index (FLI). The FLI provides an index of leptin action and bioavailability, with higher concentration of free LEP suggesting reduced biological action. Gender differences in fat deposition may differentiate FLI. PURPOSE: The purpose of this secondary analysis was to determine if gender and or adipose tissue distribution changes mediate FLI following 6-months (6M) of a diet and exercise weight loss program (WLP). METHODS: 6M WLP consisted of diet and lifestyle interventions of a nutritionally balanced diet (1250-1500 calories•day), weekly healthy lifestyle support meetings, and weekly progressive walking recommendations (150 min•week). Body composition assessed by DXA for total body (%FAT), truncal (TF), and non-trunk fat (NTF). Fasted blood samples were collected in the morning at baseline (0M), 3M, and 6M of participation. Batch analysis of LEP and LRe was completed via standard ELISA methods. FLI was determined as the ratio of LEP and LRe (ng•mL/ng•ml). RESULTS: 10 adults (n=7 Female, Age 55±5.5 yrs, Fat 48.6±2.1%; n=3 Male, Age 38±16 yrs, Fat 42.7±2.6%) completed the WLP. Significant reductions in %FAT, NTF and TF were found at all time points (p≤0.05). The FLI were reduced at 3M but not 6M for both groups (p≤0.05) (Female FLI 0M 7.0±2.5, 3M 4.4±4.0, 6M 3.6±3.9; Male FLI 0M 6.0±5.9., 3M 4.0±5.9, 6M 3.7±5.0). Reductions in TF from 0M to 3M (Female TF 0M 25.3±5.3, 3M 20.5±3.7 kg; Male TF 0M 34.8±7.5, 3M 27.2±12.5 kg) had an effect on FLI independent of gender, NTF had no effect. CONCLUSIONS: FLI reductions following 6M of WLP were highly varied between individuals and were achieved within the first 3M of fat loss. Changes in TF had the greatest effect on the FLI independent of gender or any other measure of fat tissue. Surprisingly, NTF had no effect on the FLI, for either gender, suggesting android pattern obesity is most likely a mediating variable of LEP biology.