What is the association between obesity and insulin resistance in youth and its production of colon-derived acetate, gut-derived hormone secretion, and adipose tissue lipolysis?

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMMay 11 2023

In a recent study published in the JAMA Network Open Journal, researchers assessed whether insulin resistance and adiposity in youth were linked to the fermentation of dietary fibers in the colon, secretion of gut-derived hormones, rate of production of acetate, and adipose tissue lipolysis.

 Study: Comparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity. Image Credit: Neirfy/Shutterstock.com

Background

Obesity is an increasingly concerning issue among children and adolescents, with nearly 20% of the pediatric population in the United States being affected by obesity.

It is a complex disorder influenced by environmental and behavioral factors and genetic background. Furthermore, metabolic changes, including insulin resistance in obese individuals, exacerbate the condition and result in cardiometabolic complications.

The intake of dietary fibers and other indigestible carbohydrates is recommended to reduce adiposity and improve metabolic conditions in individuals with obesity, and the beneficial effects are thought to be exerted through colonic fermentation.

The gut bacteria metabolize the fibers and other undigested carbohydrates, resulting in colonic fermentation and short-chain fatty acid (SCFA) production, with acetate being the most abundant SCFA.

A previous study by the same team of researchers reported that non-obese youth had a higher rate of acetate production than obese youths, which was linked to de novo lipogenesis in the liver.

About the study

In the present study, the researchers expanded on their earlier work by examining the association between colonic fermentation and factors such as ghrelin levels, peptide tyrosine (PYY), active glucagon-like peptide 1 (GLP-1), insulin clearance, and adiposity in youth.

Specifically, they examined how the effect of colonic fermentation on enteroendocrine secretion, insulin clearance, and lipolysis of adipose tissue could be associated with insulin resistance and adiposity.

Participants were recruited to the study if they were between the ages of 15 and 22 years and had a body mass index (BMI) between the 25^th and 75^th percentile or above the 85^th percentile for their sex and age.

Individuals on medication for chronic conditions who had used antibiotics in the last three months consumed alcohol, were pregnant, or had dietary restrictions were excluded from the study.

The participants were grouped according to three phenotypes based on insulin sensitivity and BMI percentile — obese and insulin sensitive (OIS), obese and insulin-resistant  (OIR), and lean.

The primary outcomes were the response of ghrelin, PYY, active GLP-1, and free fatty acids (FFA) to the colonic fermentation of lactulose.

Measured secondary outcomes included the production of colon-derived acetate, methane, and hydrogen, the insulin sensitivity of adipose tissue, and responses to the secretion and clearance of insulin.

The researchers hypothesized that the youth in the OIS, OIR, and lean groups would respond differently to colonic lactulose fermentation, and insulin resistance would exacerbate the differences in acetate production rates between lean and obese groups.

Furthermore, the response to colonic fermentation in the three groups concerning changes in concentrations of ghrelin, PYY, FFA, active GLP-1, and fatty tissue insulin resistance were also hypothesized to be different.

Results

The results reported that though the extent of colonic fermentation after the ingestion of lactulose was comparable in lean, OIS, and OIR groups, the rate of acetate increase was lower in the OIR youth than the ones in the other two groups.

Furthermore, although the lactulose ingestion improved adipose tissue insulin sensitivity, the OIR youth showed blunted improvements.

Investigation of enteroendocrine responses associated with lactulose ingestion and colonic fermentation revealed an increase in active GLP-1 and PYY and a decrease in ghrelin, but the researchers believe that the ghrelin and PYY responses might be influenced by insulin resistance and adiposity.

The study reported that since the extent of colonic fermentation was similar among the three groups, the rate of acetate production could also be assumed to be similar, which suggested that there was a higher intake of colon-derived acetate by the liver in youth with insulin resistance, explaining the lower acetate levels in plasma.

Additionally, the adipose tissue insulin sensitivity and changes in the levels of FFA also indicated a link between adipose tissue lipolysis and colonic fermentation.

Conclusions

Overall, the findings reported that when comparing the lean and obese but insulin-sensitive youth, obese youth with insulin resistance showed lower clearance and greater secretion of insulin, a lower rate of acetate production, diminished adipose tissue insulin sensitivity improvements, and reduced anorexigenic hormone response after lactulose ingestion.

This suggested that even as early as adolescence, the occurrence of insulin resistance along with obesity significantly reduces the benefits of the consumption of indigestible carbohydrates such as dietary fibers.