Cerebrospinal fluid and plasma leptin dynamics following bariatric surgery in women

CONTEXT: Impaired brain leptin transport is proposed as a mechanism in obesity-related leptin resistance. OBJECTIVES: We sought to evaluate plasma and cerebrospinal fluid (CSF) leptin dynamics before and 1 year after bariatric surgery (BS) and to explore their relationship with short-term weight loss and mid-term weight trajectories. METHODS: In this prospective longitudinal cohort study conducted between 2017 and 2025 at a tertiary hospital, we included 33 women with obesity eligible for BS (OB-group) and 13 age-matched control women (HC-group). Study procedures were conducted at baseline and 1 year after BS, including dual-energy x-ray absorptiometry body composition analysis and plasma/CSF sampling. Leptin levels were measured, and the CSF-to-plasma leptin ratio was calculated to assess brain leptin transport efficiency. OB-group participants were followed annually for 4 years, with body weight recorded at each visit. Weight change from year 1 to 4 was calculated, along with weight regains (WR) from nadir weight to year 4. RESULTS: At baseline, the OB-group exhibited elevated plasma and CSF leptin concentrations and reduced CSF-to-plasma leptin ratio. Following BS, leptin transport efficiency markedly improved. Although both plasma and CSF leptin decreased, the CSF leptin reduction was less pronounced. Neither baseline CSF leptin nor the CSF-to-plasma leptin ratio predicted weight loss at 1 year. Postsurgical CSF leptin levels and CSF-to-plasma leptin ratio were not associated with post-BS mid-term weight trajectories. CONCLUSION: Our findings indicate that obesity-related alterations in leptin transport are primarily attributable to the obese state rather than an intrinsic defect of the transport system and are potentially reversible through weight loss.