Effect of Weight Gain and Weight Loss on In Vivo Colonocyte Proliferation Rate in People with Obesity

Abstract

Objective To evaluate the effects of diet-induced changes in energy balance and body weight on in vivo colonocyte fractional proliferation rates (FPR) in people with obesity. Methods In vivo colonocyte FPR was assessed in 31 men and women with obesity (BMI: 35.4±4.0 kg/m2, age: 52.6±8.9 years) before and after diet-induced weight loss, weight gain, or weight maintenance. Subjects ingested aliquots of 2H2O (heavy water) daily for 4-7 days, followed by flexible sigmoidoscopy with colon biopsies to assess the incorporation of 2H into the DNA of dividing colonocytes. Results Colonocyte FPR averaged 12.7±3.8 % per day, and correlated directly with adipose tissue (IAAT) volume (r=0.364, P=0.044). Colonocyte FPR decreased in the weight loss group, did not change in the weight maintenance group, and increased in the weight gain group. The change in colonocyte FPR correlated directly with the percent change in body weight (r=0.409, P=0.028) and IAAT volume (r=0.598, P=0.001). Conclusions A high-calorie diet and weight gain increase, whereas a low-calorie diet and weight loss decrease, in vivo colonocyte proliferation rate in people with obesity. These results suggest that changes in energy balance influence the risk of developing colon cancer in people with obesity by regulating colonic mucosal growth rates.

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

“…In agreement with our findings, published epidemiological studies have provided little evidence for positive associations of short-term weight gain with colorectal cancer, 8,10,22,35 but an inverse association has been reported with intentional weight loss, 25 which we have observed for weight loss from OW to NW BMI category. Although mechanistic studies have shown that colonocyte proliferation increases with weight gain and decreases with weight loss, 36 it has also been suggested that weight gain in middle adulthood is less hazardous for colorectal cancer compared to weight gain during early adulthood. 8,37 This might be related to different causes of weight gain levels of leptin and pancreatic cancer has been reported in men, 41 while exogenous oestrogens have shown a protective effect against pancreatic cancer in women.…”

“…In agreement with our findings, published epidemiological studies have provided little evidence for positive associations of short-term weight gain with colorectal cancer, 8,10,22,35 but an inverse association has been reported with intentional weight loss,25 which we have observed for weight loss from OW to NW BMI category. Although mechanistic studies have shown that colonocyte proliferation increases with weight gain and decreases with weight loss,36…”

Berberine inhibits adipocyte differentiation, proliferation and adiposity through down-regulating galectin-3

“…The excessive differentiation or proliferation of adipocytes will cause an increase of their size or number, an expansion of adipose tissue, and obesity 1 . The prevalence of obesity has increased worldwide and obesity will increase the risks of metabolic diseases, cardiovascular diseases, and cancer 2–4 . Therefore, the research and development of novel anti-obesity drugs are of significant scientific as well as clinical importance.…”

The basis and design for time‐restricted eating compared with daily calorie restriction for weight loss and colorectal cancer risk reduction trial (TRE‐CRC trial)

“…Cal‐R can reduce body weight, decrease insulin resistance, and lower chronic inflammation, all of which are associated with the development of CRC [ 5 , 7 ]. However, only a few studies have examined the effect of Cal‐R on the colon tissue among individuals with obesity [ 8 , 9 , 10 ]. Among 10 participants with obesity, Pendyala et al [ 9 ] found that medically supervised Cal‐R was associated with reduced tissue inflammation (e.g., CD3, CD163) and downregulation of cancer‐related gene pathways (e.g., signal transducer and activator of transcription, nuclear factor‐κB).…”