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Context Obesity is widely regarded as an established risk factor for colorectal cancer (CRC). However, recent studies have shown that lower mortality and better cancer-specific survival were observed in CRC patients with elevated body mass index (BMI), an example of the obesity paradox, which is the inverse correlation between obesity and mortality in some populations. Objective The aim of this systematic review and meta-analysis was to investigate the association between BMI and CRC outcomes. Data Sources PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase databases were searched for relevant articles published from inception to December 31, 2020. Study Selection Studies comparing the prognosis of CRC patients with obesity or overweight with that of normal-weight CRC patients were eligible. Data Extraction Data were extracted by 2 reviewers independently; differences were resolved by a third reviewer. BMI was classified according to WHO categories. Data Analysis To assess the prognostic effects of different BMI categories in CRC patients, hazard ratios and 95%CIs of overall survival, disease-free survival, and cancer-specific survival were extracted from included articles. Results Sixteen studies (55 391 patients in total) were included. Higher BMI was significantly associated with more favorable CRC outcomes. Compared with normal-weight patients, underweight patients had worse overall survival (HR = 1.26; 95%CI, 1.15–1.37) and disease-free survival (HR = 1.19; 95%CI, 1.11–1.27, while patients with overweight had better overall survival (HR = 0.92; 95%CI, 0.86–0.99), disease-free survival (HR = 0.96; 95%CI, 0.93–1.00), and cancer-specific survival (HR = 0.86; 95%CI, 0.76–0.98). Patients with morbid obesity had worse overall survival (HR = 1.12; 95%CI, 1.02–1.22) and disease-free survival (HR = 1.15; 95%CI, 1.07–1.24) than normal-weight patients. There was no significant difference in cancer-specific survival between patients with obesity (HR = 0.94; 95%CI, 0.76–1.16) and patients with normal weight, nor between patients with underweight and patients with normal weight (HR = 1.14; 95%CI, 0.82–1.58). Conclusions CRC patients with a higher BMI appear to have reduced mortality compared with normal-weight CRC patients, even though higher BMI/obesity is an established determinant for the development of CRC. Systematic Review Registration PROSPERO registration no. CRD42020202320.

Long-term exercise-induced metabolic adaptations occupy a central position in exercise-afforded cardiac benefits. Emerging evidence suggests that branched-chain amino acid (BCAA) catabolic defect contributes to cardiac dysfunction in multiple cardiometabolic diseases. However, the role of BCAA catabolism in exercise-afforded cardiac benefits remains unknown. Here, we show that exercise improves BCAA catabolism and thus reduce cardiac vulnerability to myocardial ischemic injury. Exercise increased circulating BCAA levels in both humans (male adolescent athletes) and mice (following an 8-week swimming intervention). It increased the expression of mitochondrial localized 2C-type serine-threonine protein phosphatase (PP2Cm), a key enzyme in regulating BCAA catabolism, and decreased BCAA accumulation in mouse hearts, indicating an increase in BCAA catabolism. Pharmacological promotion of BCAA catabolism protected the mouse heart against myocardial infarction (MI) induced by permanent ligation of the left descending coronary artery. Although cardiac-specific PP2Cm knockout showed no significant effects on cardiac structural and functional adaptations to exercise, it blunted the cardioprotective effects of exercise against MI. Mechanistically, exercise alleviated BCAA accumulation and subsequently inactivated the mammalian target of rapamycin in MI hearts. These results showed that exercise elevated BCAA catabolism and protected the heart against myocardial ischemic injury, reinforcing the role of exercise in the promotion of cardiac health.