Lipolysis defect in people with obesity who undergo metabolic surgery

Abstract

Objective: Cross-sectional studies demonstrate that catecholamine stimulation of fat cell lipolysis is blunted in obesity. We investigated whether this defect persists after substantial weight loss has been induced by metabolic surgery, and whether it is related to the outcome.

Design/methods: Patients with obesity not able to successfully reduce body weight by conventional means (n = 126) were investigated before and 5 years after Roux-en-Y gastric bypass surgery (RYGB). They were compared with propensity-score matched subjects selected from a control group (n = 1017), and with the entire group after adjustment for age, sex, body mass index (BMI), fat cell volume and other clinical parameters. Catecholamine-stimulated lipolysis (glycerol release) was investigated in isolated fat cells using noradrenaline (natural hormone) or isoprenaline (synthetic beta-adrenoceptor agonist).

Results: Following RYGB, BMI was reduced from 39.9 (37.5-43.5) (median and interquartile range) to 29.5 (26.7-31.9) kg/m² (p < 0.0001). The post-RYGB patients had about 50% lower lipolysis rates compared with the matched and total series of controls (p < 0.0005). Nordrenaline activation of lipolysis at baseline was associated with the RYGB effect; those with high lipolysis activation (upper tertile) lost 30%-45% more in body weight, BMI or fat mass than those with low (bottom tertile) initial lipolysis activation (p < 0.0007).

Conclusion: Patients with obesity requiring metabolic surgery have impaired ability of catecholamines to stimulate lipolysis, which remains despite long-term normalization of body weight by RYGB. Furthermore, preoperative variations in the ability of catecholamines to activate lipolysis may predict the long-term reduction in body weight and fat mass.

Keywords: Roux-en-Y gastric bypass; adipocytes; catecholamines; glycerol.

Fig. 1

Patient inclusion process. Flow chart for recruiting and investigating patients in the two Roux‐en‐Y gastric bypass (RYGB) studies.

Fig. 2

Findings with lipolysis. Lipolysis is expressed as μmoles of glycerol release per 2 h. (a–c) Lipolysis per gram of lipids. (d–f) Lipolysis per 10⁷ fat cells. Fat cells were incubated in the basal state (a,d) with noradrenaline (NA, b,e) or isoprenaline (ISO, c,f). Results before and 5 years after Roux‐en‐Y gastric bypass (RYGB) were compared by paired sign test. Control persons were compared with RYGB patients who did not return for 5‐year re‐examination (noncompleters) and with RYGB completers before surgery using the Wilcoxon test.

Fig. 3

Propensity‐score matching. Control subjects were matched in the ratio 2:1 to Roux‐en‐Y gastric bypass patients, 5 years after surgery. The graph shows the covariate balance by standardized mean differences before (unadjusted—yellow dots) and after (adjusted—green dots) propensity‐score matching for the parameters listed on the left of the graph.

Fig. 4

Prediction of Roux‐en‐Y gastric bypass outcome from initial lipolytic activity. Noradrenaline/basal lipolysis at baseline was compared with the difference between values at baseline minus at 5 years (delta) for body weight (a,d), body mass index (b,e) or fat mass (c,f). Spearman's rank correlation or the Wilcoxon test was used for statistical analysis.