Association of Laparoscopic Gastric Bypass Surgery With Telomere Length in Patients With Obesity

Abstract

This study examines whether telomeres lengthen in obese patients before and after laparoscopic gastric bypass surgery.

Severe obesity is the leading public health crisis in the industrialized world and affects men and women of all races/ethnicities and socioeconomic status.¹ Along with obesity, aging-related dementia risk factors include insulin resistance, lipid abnormality, and inflammation.^2,3 Other age-related changes include telomere shortening, which has implications such as genomic instability and cancer and has been shown to be associated with high body mass index (calculated as weight in kilograms divided by height in meters squared).⁴ Telomeres are repeating strands of DNA that flank mammalian chromosomes and thus protect coding DNA from progressive degradation after each replication. In the peripheral blood, telomeres progressively shorten with the aging process and have a negative correlation with oxidative stress and a severe inflammatory state.^3,4 Data are currently mixed on the association between surgical weight loss and telomere length.^5,6 Our primary goal in this study was to examine whether telomeres lengthen in obese patients before and after laparoscopic gastric bypass surgery.

Methods

Fifty-one patients underwent laparoscopic gastric bypass surgery at an accredited academic institution. Telomere length and biochemical cardiac risk factors (levels of total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and high-sensitivity C-reactive protein [CRP]) were evaluated preoperatively and at 3, 6, and 12 months postoperatively. Quantitative polymerase chain reaction was used to create a relative telomere to single copy gene (T/S) ratio, which is proportional to mean telomere length. According to standard protocol at Telomere Diagnostics Inc, genomic DNA from 200 μL of whole blood was purified with a QIAamp DNA Blood Mini Kit (Qiagen) and then quantified by a NanoDrop 8000UV-Vis Spectrophotometer (Thermo Fisher Scientific). The genomic DNA samples were diluted with low EDTA Tris hydrochloride, resulting in a DNA concentration of 12.5 ng/μL in working plates. A t test, χ² analysis, and Spearman and Pearson correlations were used to analyze data. A 2-sided P < .05 was considered to be statistically significant. Patients provided written informed consent, and all data were deidentified. The study was approved by the Stanford University Institutional Review Board.

Results

The demographic distribution in the 51 patients in this study (mean age, 48.6 years; age range, 19.0-68.0 years; 39 [76%] female) was representative of the overall population undergoing bariatric surgery. By 12 postoperative months, the mean body mass index reduction was 12.2, and the amount of excess weight loss was 70.4% (P = .01). In addition, the following cardiometabolic risk factor means changed from before to 12 months after the operation: CRP level, 6.7 to 3.6 mg/L (P = .12) (to convert to nanomoles per liter, multiply by 9.524; LDL-C level, 96.8 to 102 mg/dL (P = .58) (to convert to millimoles per liter, multiply by 0.0259); and HDL-C level, 45.3 to 56.3 mg/dL (P = .004) (to convert to millimoles per liter, multiply by 0.0259).

For all patients, mean telomere length was not statistically different from before (0.987) to 12 months after the operation (0.982) (P = .76). However, when patients were categorized by inflammatory and lipid markers, significant differences in telomere length emerged over time. Patients with a preoperative LDL-C level greater than 140 mg/dL had significant telomere lengthening compared with patients with low LDL-C levels (−0.0271 [normal LDL-C] vs +0.0227 [abnormal LDL-C], P = .04). Preoperatively, the mean CRP level for all patients was 7 mg/L. Patients with a preoperative CRP level of greater than 7 mg/L had significant telomere lengthening compared with patients with low CRP levels (−0.02294 [low CRP] vs +0.04125 [high CRP], P = .005) (Figure). Furthermore, in the group of patients with high CRP levels, a significant positive correlation was found between weight loss and telomere length (r = 0.879, P = .0498) as well as between change in HDL-C level and increase in telomere length (r = 0.842. P = .02).

Figure. One-Year Change in Telomere Length.

Quantitative polymerase chain reaction was used to create a relative telomere to single copy gene ratio, which is proportional to mean telomere length. CRP indicates high-sensitivity C-reactive protein; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Conclusions

In this study, surgical weight loss was associated with lengthening of telomeres in patients who had an adverse cardiometabolic state before surgery. Although this study is limited by the small study population and a single site intervention, this finding suggests that the greatest potential benefit for slowing the aging process as expressed by telomere lengthening is in patients with the most comorbidity before surgery. Further study is needed with greater numbers and diversity of procedures. Finally, the study demonstrated an association among obesity, inflammation, and the aging process.