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Long-Term Prospective and Controlled Studies Demonstrate Adipose Tissue Hypercellularity and Relative Leptin Deficiency in the Postobese State

Karolinska Institutet, Clinical Research Center and Department of Medicine, Karolinska University Hospital, SE-141 86 Huddinge, Stockholm, Sweden

Address all correspondence and requests for reprints to: Peter Arner, Professor, M.D., Ph.D., Department of Medicine, Karolinska University Hospital Huddinge, SE-141 86 Huddinge, Stockholm, Sweden. E-mail: peter.arner{at}medhs.ki.se.

Context: Enlarged fat cells and leptin hypersecretion are hallmarks of common obesity.

Objective: The objective of this study was to investigate fat cell size and leptin production in the basal state after long-term steady-state weight reduction to the nonobese state.

Design: This prospective case-control study had a duration of 3 ± 1 (mean ± SD) yr.

Patients: Twenty-five obese women (cases) were studied. Each case was compared with a control subject matched for age, sex, and body mass index (BMI) at nadir of weight for the cases.

Setting: This study was conducted at Karolinska University Hospital (Stockholm, Sweden).

Intervention: The subjects were followed until they reached a steady-state weight reduction after lifestyle modification or bariatric surgery (cases). Treatment target was the nonobese state (BMI < 30 kg/m²). Subcutaneous adipose tissue secretion of leptin, serum leptin levels, and fat cell volume were determined after an overnight fast.

Results: Ten obese women (40%) reached the nonobese state. This was accompanied by marked decreases in fat cell volume, leptin secretion, and serum leptin concentrations (P < 0.0001). The postobese cases had 43% smaller fat cell volume (P = 0.0008), 68% lower adipocyte leptin production (P = 0.001), and 54% lower serum leptin levels (P = 0.0007) than control subjects, despite almost identical percent body fat in the two groups. Fat cell volume, but not percent body fat or BMI, was directly proportional to leptin secretion and serum leptin concentrations.

Conclusion: Adipose tissue hyperplasia (too many small fat cells) and low leptin production resulting in relative hypoleptinemia in the fasting (basal) state are common features of the postobese state in women.

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