Fibrosis in Fat Tissue Predicts Poor Weight Loss After Surgery

Becky McCall

September 12, 2017

LISBON, PORTUGAL — A novel and easy-to-use score that measures fibrosis in human subcutaneous adipose tissue (scAT) could help to identify patients who are poor responders to Roux-en-Y gastric bypass (RYGB) weight-loss surgery, the results of a trial that could lead to more personalized follow-up care indicate.

In particular, severely obese subjects with a fibrosis score of adipose tissue (FAT) score of at least 2 prior to bariatric surgery showed the greatest risk of poor response after the operation.

"We found that the most severe fibrosis scores before surgery were associated with a poorer weight-loss response of three to four times the risk," reported Dr Pierre Bel Lassen, MD, from INSERM and Pitié-Salpêtrière Hospital, Assistance Publique– Hôpitaux de Paris (APHP), France, who presented the findings at the European Association for the Study of Diabetes (EASD) 2017 Annual Meeting.

The study was also published recently in the Journal of Clinical Endocrinology and Metabolism.

The results showed that at 1 year after bariatric surgery, patients with a high FAT score (≥2), after adjustment for age, diabetes status, hypertension, interleukin-6 level, and percentage fat mass, had an odds ratio of 3.6 (= .003) of being a "poor responder."

Poor responders lost an average 22.7% of body weight compared with 35.6% in good responders, corresponding to an average difference of 17 kg.

Need for a New Predictive Score

The researchers say there is a need for a novel, easy-to-use score for predicting response to bariatric surgery.

"It is important to find the predictive factors for who will be a poor responder to bariatric surgery before the intervention," Dr Bel Lassen pointed out, adding that previously identified factors associated with low weight loss include older age, diabetes, and hypertension, as well as psychological factors including eating disorders.

However, he noted, "If we pool these presurgery factors it predicts only 14% of postbariatric weight loss. There's a need to improve on this." Prior studies had not considered the potential of structural alterations to adipose tissue.

Previously, the other main method for predicting outcome postsurgery involved color detection of collagen laid down in the adipose tissue, but "this is time consuming, depends on slide quality, and is affected by heterogeneity of fibrosis. We wanted to create a simple, semiquantitative score of scAT that would be reproducible in routine clinics and help predict bariatric-surgery outcomes," Dr Bel Lassen explained.

Essentially, the aims of the study were twofold: first, to create a simple, histological score to easily characterize scAT fibrosis, similar to diagnostic scoring of nonalcoholic fatty liver disease (NAFLD). Second, the work aimed to investigate the clinical applicability of the FAT score in predicting postsurgical weight loss.

The FAT score was used to characterize 183 biopsy specimens from severely obese patients who had received RYGB surgery and who had complete follow-up data 1 year after surgery. Mean patient age was 43 years, with an average body mass index (BMI) of 47 kg/m2, 76% were women, and 39% of patients had diabetes.

Poor response to RYGB surgery was defined as < 28% of total weight loss at 1 year (lowest tertile).

Drawing on the parallel with liver disease, the methods used in the development of the FAT score were similar to those used in the design of NAFLD histological score.

Structural Changes to Adipose Tissue in Obesity

Adipose tissue fibrosis has gained recognition as an important pathological alteration during the development of obesity, explain the researchers.

Its structure becomes dysfunctional and progressively fibrotic as collagen accumulates around the lobules of adipose tissue, reducing plasticity. The FAT score is based on these structural changes in scAT.

"Our FAT score is based on a semiquantitative evaluation of perilobular and pericellular fibrosis and is easily measured and reproducible," said Dr Bel Lassen, adding that the relationship between the total scAT fibrosis and the amount of fibrosis shows a P for trend of <0.001.

The French clinician-researcher reiterated that weight-loss outcome after bariatric surgery depends on a combination of biological factors and psychological aspects and noted, "The latter are sometimes difficult to evaluate and integrate into a predictive score."

He cautioned that while their method was a significant improvement over previous attempts to determine surgical outcomes, it was found to successfully predict response for only 72% of patients.

Commenting on the study, Jan Eriksson, MD, an endocrinologist from Uppsala University, Sweden, said that the work clearly had value in seeking to find a measure to predict who will benefit from bariatric surgery or not, but it is also interesting from a pathobiology perspective.

"There is a trend for diabetes patients to have a higher fibrosis score, so their adipose tissue might have a different morphology [from those who are simply obese] linked to metabolic problems," he remarked.

However, he also noted, "It is surprising that there was an increase in the fibrosis score following bariatric surgery…I would have expected the opposite, and this needs further research. Potentially this could have clinical use, but right now it is mostly interesting for the pathophysiology."

Dr Bel Lassen and Dr Eriksson have declared no relevant financial relationships.

J Clin Endocrinol Metab. 2017;102:2443–2453. Article

European Association for the Study of Diabetes (EASD) 2017 Annual Meeting. September 12, 2017, Lisbon, Portugal. Oral presentation 32

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