WISER Survivor Trial: Combined Effect of Exercise and Weight Loss Interventions on Adiponectin and Leptin Levels in Breast Cancer Survivors with Overweight or Obesity

Abstract

Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to leptin (A:L) ratio. The four-arm randomized controlled WISER Survivor trial examined the 12-month intervention effects of exercise, weight loss, and the combination of exercise and weight loss on adipokine levels among breast cancer survivors (n = 339) with overweight or obesity. Compared with Control, the Combination of Exercise and Weight Loss decreased leptin levels (−35.9%; 95% CI: −46.8%, −25.0%) and increased A:L ratio (11.6%; 95% CI: 5.6%, 17.6%) but did not change adiponectin levels (4.1%; 95% CI: −3.1%, 11.2%). Compared with Control, Weight Loss Alone decreased leptin levels (−35.6%; 95% CI: −46.6%, −24.5%) and increased A:L ratio (10.6%; 95% CI: 4.7%, 16.5%) but did not change adiponectin levels (0.9%; 95% CI: −6.0%, 7.9%). Compared with Control, Exercise Alone did not change leptin levels, adiponectin levels, or A:L ratio. In analyses that consolidated intervention groups, compared with Control, weight loss of ≥5% decreased leptin levels (p trend < 0.01) and increased A:L ratio (p trend < 0.01) but did not alter adiponectin levels (p trend = 0.53). Weight loss, with or without exercise, was associated with decreased leptin levels in breast cancer survivors with overweight or obesity. Improvements in the adipokine secretion profile (A:L ratio) were primarily driven by a weight loss-induced change in leptin levels.

Effect of metformin and lifestyle intervention on adipokines and hormones in breast cancer survivors: a pooled analysis from two randomized controlled trials

“…Goodwin and colleagues [ 21 ] reported similar relative changes with metformin compared to placebo in their MA.32 trial, despite lower baseline leptin levels, in line with the lower median BMI in their trial. The WISER Survivor trial in overweight/obese breast cancer survivors observed significant decrements in leptin in the weight loss arms [ 22 ]. Adiponectin favorably increased only in the lifestyle intervention group.…”

Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity

“…Exercise could be an easy and effective approach to stimulate the secretion of adiponectin, BDNF, and GLP-1 in both nonobese and obese individuals. Several studies have shown that consistent exercise can increase the levels of adiponectin [ 51 ], BDNF [ 52 ], and GLP-1 [ 53 ] in the blood of both nonobese and obese people.…”