OBJECTIVES: Obesity (body mass index (BMI) ≥ 30 kg/m²) is usually presented with structural and functional hypothalamic dysfunction. However, it is currently unclear whether weight loss can modify these hypothalamic changes. We, therefore, aimed to conduct a systematic review and meta-analysis to determine the effect of body mass reduction in obese individuals on hypothalamic structure and function.

METHODS: PubMed, Embase and Cochrane databases were searched through 11/2020 for studies that evaluated the change in hypothalamic structure and function after weight loss. Qualitative and quantitative analyses were performed on reported magnetic resonance imaging techniques, medio-basal hypothalamus T2-relaxation time, blood oxygen level dependent (BOLD) contrast, voxel-based morphometry (VBM), and biomarkers including glucose, insulin, leptin, ghrelin, and interleukins. Mean differences pre- vs. post-weight loss and 95% confidence intervals (CI) were pooled using random-effects models.

RESULTS: Thirteen pre-post studies were included, of which six accounted for the meta-analysis. A favorable decrease in T2-relaxation time (one study) and BOLD contrast showed a favorable change in neural and functional activity of the hypothalamus after weight loss (four studies), with higher peak activities after surgical weight loss (two studies). No difference was found in VBM in the gray matter density of the hypothalamus after surgical weight loss (one study). Pooled mean differences pre- vs. post-surgical weight loss revealed a decrease of 8.53 mg/dl (95% CI: 5.17, 11.9; six studies) in glucose; 7.73 pmol/l (95% CI: 5.07, 10.4; four studies) in insulin; 15.5 ng/ml (95% CI: 9.40, 21.6; four studies) in leptin, 142.9 pg/ml (95% CI: 79.0, 206.8; two studies) in ghrelin, and 9.43 pg/ml (95% CI: -6.89, 25.7; two studies) in IL6.

CONCLUSIONS: Our results demonstrated that weight reduction in obesity escalated the activity of hypothalamus and upregulated body homeostasis along with improved markers related to metabolic regulation.