Science Spotlight

Measuring the metabolic effects of bariatric surgery

From the Kratz Lab, Public Health Sciences Division.

More than 36% of US adults are obese. As obesity is associated with higher risk for developing cardiovascular disease, diabetes, and many forms of cancer, the obesity epidemic is a major public health threat. Obesity is thought to contribute to these diseases at least partly through a state of chronic, low-grade inflammation, particularly in the expanded fat or adipose tissue. While the cause of this inflammation is still unknown, it is hypothesized that adipose tissue inflammation may contribute to the development of insulin resistance. Bariatric surgery is one approach that can be successful for helping individuals lose weight, but its impact on adipose tissue inflammation is unclear. In a recent issue of Metabolism, Drs. Derek Hagman and Mario Kratz in the Public Health Sciences Division at Fred Hutch measured metabolic and inflammatory markers in the adipose tissue and blood of patients before and after bariatric surgery. The authors found both short- and long-term metabolic improvements, but no significant reductions in adipose tissue inflammation.

To measure these metabolic and inflammatory markers, the authors conducted a prospective clinical study of 14 obese men and women who were scheduled to have bariatric surgery – either gastric bypass or vertical sleeve gastrectomy. These participants provided samples of blood and subcutaneous adipose tissue at three time points: 1-2 weeks prior to their surgery, 4-6 weeks after their surgery, and 6-12 months after their surgery. A wide range of metabolic and inflammatory measurements were evaluated from these samples, including an oral glucose tolerance test to assess glucose tolerance and insulin sensitivity. The authors also conducted immunophenotyping of adipose tissue immune cells, and measured adipose tissue gene expression of genes related to inflammation. These values were then evaluated for changes over time in relationship to bariatric surgery.

Diagram of effects of bariatric surgery
Obesity is associated with low-grade chronic inflammation in the expanded fat tissue (adipose tissue), which is thought to be a trigger of insulin resistance leading to glucose intolerance and type 2 diabetes mellitus. Bariatric surgery had been shown previously to reduce body weight substantially, and to reduce insulin resistance and glucose intolerance. In many patients, these effects led to complete and lasting remission from type 2 diabetes mellitus. This study addressed the question of whether the effect of bariatric surgery on insulin resistance may be mediated by a reduction in low-grade chronic adipose tissue inflammation. In contrast to the investigators’ hypothesis, there was no evidence of a reduction in adipose tissue inflammation after bariatric surgery, neither in the short term nor many months after the surgery when participants had lost – on average – more than 75 pounds of body weight. Image from Dr. Mario Kratz

As expected, these bariatric surgeries led to substantial weight loss in these participants, who lost an average of 30 pounds in the first month after surgery, and 77 pounds in the first year. Metabolic profiles were also rapidly improved, with substantial improvements in glucose tolerance that were largely due to improved insulin production by pancreatic beta-cells within the first month. These improvements occurred in spite of increased leukocyte infiltration of the adipose tissue, with the number of neutrophils increasing 15- to 20-fold. No significant reduction was seen in the adipose tissue expression of genes encoding major mediators of inflammation. The longer-term metabolic improvements that were observed after participants had lost even more weight at 6-12 months post surgery, which included improved insulin sensitivity, were also not associated with reduced subcutaneous adipose tissue inflammation. Biomarkers of inflammation in blood, such as C-reactive protein, were unchanged at one month, but reduced with the greater weight loss 6-12 months after surgery. Secondary analyses suggested that the improvements in metabolic status appeared to be largely driven by weight loss.

Together with previous findings (see Kratz et al., 2016), “our work clearly shows that metabolic improvements in response to bariatric surgery are not associated with a reduction in low-grade chronic adipose tissue inflammation,” said senior author Dr. Kratz. “This is very surprising, because obesity is strongly associated with adipose tissue inflammation, and it would have been plausible to think that the inflammation would be at least attenuated in response to the substantial weight loss following bariatric surgery.”

Instead, said Kratz, “our data also cast some doubt on the hypothesis that the low-grade chronic inflammation is a major cause of insulin resistance, because insulin resistance was substantially reduced 6-12 months following bariatric surgery, even though adipose tissue inflammation persisted unchanged from baseline. Given that much of the data on the relationship between inflammation and insulin resistance is from rodent models of obesity, our data suggest that we need to learn more about that relationship in humans.”

Continued research in this space will hopefully begin to shed light on the complex relationships between these metabolic and inflammatory mechanisms in obesity, but will require answering several outstanding questions. Said Kratz, “one key question that remains is through which mechanisms bariatric surgeries have such a massive impact on insulin sensitivity and glucose tolerance. Another is related to the nature of the relationship between adipose tissue inflammation and insulin resistance in humans. The data we now generated are just hard to reconcile with the reigning paradigm that adipose tissue inflammation causes insulin resistance.”



Also contributing to this manuscript from the Fred Hutch were Drs. Ilona Larson, Jessica Kusma, Gail Cromer, and Karen Makar. 

Funding for this study was provided by the National Cancer Institute (NIH), the American Diabetes Association, the University of Washington Diabetes Research Center, and the University of Washington Institute of Translational Health Sciences.



Hagman DK, Larson I, Kuzma JN, Cromer G, Makar K, Rubinow KB, Foster-Schubert KE, van Yserloo B, Billing PS, Landerholm RW, Crouthamel M, Flum DR, Cummings DE, Kratz M. The short-term and long-term effects of bariatric/metabolic surgery on subcutaneous adipose tissue inflammation in humans. Metabolism 2017; 70:12-22. doi: 10.1016/j.metabol.2017.01.030. 

Kratz M, Hagman DK, Kuzma JN, Foster-Schubert KE, Chan CP, Stewart S, van Yserloo B, Westbrook EO, Arterburn DE, Flum DR, Cummings DE. Improvements in glycemic control after gastric bypass occur despite persistent adipose tissue inflammation. Obesity 2016; 24(7):1438-45. doi: 10.1002/oby.21524.