Key pathway and gene alterations in the gastric mucosa associated with obesity and obesity-related diabetes.

BACKGROUND AND OBJECTIVE: The stomach plays an important role in obesity and obesity-related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes. METHODS: We performed gene microarray and real time-polymerase chain reaction (RT-PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes. RESULTS: In total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co-regulated in both comparisons. Seven differentially expressed genes were validated by RT-PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G-protein coupled receptor biological processes, and primarily participated in the PI3K-Akt and AGE-RAGE signaling pathways. CONCLUSIONS: Obesity and obesity-related diabetes are associated with important gene expression and pathway alterations in the stomach.

Gender difference in the relationship between serum uric acid reduction and improvement in body fat distribution after laparoscopic sleeve gastrectomy in Chinese obese patients: a 6-month follow-up.

BACKGROUND: Hyperuricemia is related to obesity and fat accumulation. This study aimed to observe the effects of laparoscopic sleeve gastrectomy (LSG) on serum uric acid (sUA) level and body fat distribution in obese patients. The relationships between post-LSG improvement in sUA levels and body fat distribution changes, as well as their sex-related differences, were also explored. METHODS: In total, 128 obese patients (48 men; 80 women) who underwent LSG were enrolled. Anthropometric indicators, glucose and lipid metabolic indicators, and sUA levels were measured pre-LSG and 6 months post-LSG. The body compositions were measured via dual-energy X-ray absorptiometry. The patients were divided into normal-sUA (NUA) and high-sUA (HUA) groups based on preoperative sUA levels. RESULTS: Compared with the NUA group, the reduction of sUA levels 6 months post-LSG was more significant in the HUA group. In addition, sUA reduction in the female HUA group was more significant than that of the male HUA group (P < 0.01). Changes in serum uric acid levels (ΔsUA) in the male HUA group was positively correlated with changes in body weight, body mass index, neck circumference, and hip circumference (r = 0.618, 0.653, 0.716, and 0.501, respectively; P < 0.05 in all cases). It was also positively correlated with changes in fat mass in the gynoid region, android region, and legs, (r = 0.675, 0.551, and 0.712, respectively; P < 0.05 in all cases), and negatively correlated with changes in total testosterone (ΔTT) (r = - 0.517; P = 0.040). Furthermore, ΔTT in this group was closely associated with the improved sex-related fat distribution. The ΔsUA in the female HUA group was positively correlated with changes in fasting serum C peptide and ΔLNIR (r = 0.449 and 0.449, respectively; P < 0.05 in both cases). In addition, it was also positively correlated with changes in visceral adipose tissue (VAT) fat mass, VAT fat volume, and VAT fat area (r = 0.749, 0.749, and 0.747, respectively; P < 0.01 in all cases). CONCLUSIONS: sUA levels of obese patients with hyperuricemia improved 6 months after LSG. Reduction of sUA after LSG was correlated with improved body fat distribution, and the relationships also displayed sex-based differences. Uric acid might be an important metabolic regulator associated with fat distribution and sex hormones.

Reduction in Thyroid-Stimulating Hormone Correlated with Improved Inflammation Markers in Chinese Patients with Morbid Obesity Undergoing Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: Bariatric surgery has a significant impact on levels of thyroid hormones and various inflammatory markers in obesity. The relationship between changes in thyroid hormones and inflammatory markers after bariatric surgery is unknown. We aimed to investigate the changes in thyroid hormones and their relations to inflammatory changes after laparoscopic sleeve gastrectomy (LSG) in Chinese patients with morbid obesity. METHODS: Eighty-eight patients with morbid obesity (56.8% female; age 30.9 ± 9.5 years; BMI 39.9 ± 5.7 kg/m2) submitted to LSG were selected. Patients were subdivided into euthyroid group and subclinical hypothyroidism (SH) group. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), inflammatory markers, and related metabolic indexes were analyzed pre- and 12 months post-LSG. RESULTS: SH patients presented significantly higher interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) than euthyroid patients. Twelve-month post-surgery, the SH incidence decreased from 31.8 to 2.3% (P < 0.001). TSH levels were declined significantly in both groups but were more pronounced in SH group (P < 0.001), whereas no change in FT4 in either group. Additionally, we observed marked reduction of IL-6, TNF-α, and CRP in SH group, as well as TNF-α and CRP in euthyroid group. After adjusting for age, baseline BMI, and changes in BMI, decrease in TSH correlated significantly with decreased HOMA-IR and TNF-α in euthyroid group and decreased fasting insulin (FINS), IL-6, TNF-α, and CRP in SH group. CONCLUSION: LSG promotes TSH reduction in patients with morbid obesity that is more pronounced in patients with SH and correlated with improved inflammatory state after surgery.

Changes in inflammatory markers correlated with increased testosterone after laparoscopic sleeve gastrectomy in obese Chinese men with acanthosis nigricans.

Bariatric surgery is an effective method for severe obesity and its related comorbidities. This study was performed to explore the alterations of sex hormones and inflammatory markers following laparoscopic sleeve gastrectomy (LSG) among obese Chinese men with acanthosis nigricans (AN). Sixty-five obese men who underwent LSG were enrolled, comprising simple obesity without AN (OB group, n = 20) and obesity with AN (AN group, n = 45). There were 31 healthy male controls with normal body mass index (BMI) included. Anthropometry data, inflammatory markers, sex hormones and metabolic parameters were compared preoperatively and 12 months post-operatively. At baseline, patients in the AN group were associated with more severe metabolic abnormalities than the OB and control groups. Twelve months after surgery, AN patients obtained significant improvement in skin condition and reduction in AN score. BMI, fasting insulin (FINS), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), tumor necrosis factor-α (TNF-α) and total testosterone (TT) were significantly changed in both groups, while interleukin (IL)-6, IL-8 and C-reactive protein were changed significantly only in the AN group. Moreover, FINS, HOMA-IR, TT and IL-6 levels were changed more in the AN group than those in the OB group. Multivariate regression analysis revealed that TT increase correlated significantly with reduction in FINS and HOMA-IR in both groups, but correlated with changes in IL-6 only in the AN group. In conclusion, LSG is effective in improving the skin condition of obese men with AN. The increased TT in AN patients correlated with amelioration of inflammatory state in addition to insulin resistance after LSG.

Changes in Sex Hormones After Laparoscopic Sleeve Gastrectomy in Chinese Obese Men: a 12-Month Follow-Up.

BACKGROUND: To examine changes in sex hormones after laparoscopic sleeve gastrectomy (LSG) in Chinese obese male patients and their correlation with metabolic parameters including serum uric acid (SUA) METHODS: A total of 56 obese men with body mass index (BMI) 41.9 ± 5.8 kg/m2 undergoing LSG were selected. Thirty-one healthy men with normal BMI were included as controls. Levels of total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), SUA, and other metabolic indices were compared pre- and 12 months post-LSG. Calculated free testosterone (cFT) was calculated from TT and SHBG using an empirical equation. RESULTS: At baseline, low TT and hyperuricemia (HUA) were common in obese men. Twelve months after LSG, statistically significant reduction in weight, BMI, and glucolipid metabolism indices was noted. SUA levels declined remarkably from 474.9 ± 94.6 to 338.8 ± 81.9 µmol/L and the percentage of HUA decreased from 76.8 to 54.1% (all P < 0.001). Additionally, significant increases in TT, SHBG, and cFT as well as a decrease in percentage of low TT were observed after LSG (all P < 0.05), while E2, FSH, and LH did not change significantly. Moreover, changes in TT levels were more pronounced than those of other sex hormones. After age and BMI were adjusted, increased TT levels were correlated significantly with decreased SUA (ß = - 1.077, P < 0.05), BMI (ß = - 0.712, P < 0.001), and HOMA-IR (ß = - 0.652, P < 0.05), as well as increased SHBG (ß = 0.759, P < 0.001). CONCLUSIONS: LSG promotes a significant increase in TT levels in Chinese obese men, which may be mediated by substantial weight loss, SUA reduction, and improved insulin resistance (IR).

Alterations in Fat Mass and Bone Mineral Density Are Associated with Decreased Lipocalin-2 After Laparoscopic Sleeve Gastrectomy in Obese Chinese Women.

OBJECTIVE: Lipocalin-2 (LCN2) plays an important role in the regulation of the obesity and obesity-related dysmetabolic state. This study aimed to analyze serum LCN2 level in Chinese women with obesity before and after laparoscopic sleeve gastrectomy (LSG) and determine the association between alteration in fat mass and bone mineral density (BMD) and LCN2 level. METHODS: Fifty-two women (38 patients with obesity and 14 with normal body mass index (BMI)) were enrolled in this study. All patients with obesity underwent LSG. BMDs of the arm, leg, thoracic and lumbar spine, and pelvis were measured by dual-energy X-ray absorptiometry. Body fat mass and distribution were measured by dual-energy X-ray absorptiometry, and routine anthropometric/laboratory biochemical parameters at baseline and 3 and 12 months after LSG were recorded. Serum LCN2 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Serum LCN2 level was significantly higher in women with obesity than in the controls with normal BMI (102.70 ± 27.19 vs. 80.66 ± 19.55 ng/mL, P = 0.009). LCN2 level was decreased at 3 and 12 months after LSG (86.73 ± 26.79 ng/mL, P = 0.171, and 64.79 ± 28.39 ng/mL, P < 0.001, respectively). LSG led to marked body fat mass and slight BMD decrease. Decreased LCN2 level was significantly correlated with alterations in left and right leg BMDs and trunk fat mass at 12 months after LSG. CONCLUSIONS: Obesity was associated with up-regulated serum LCN2 level. Decreased LCN2 level was positively correlated with changes in BMD and fat mass at 12 months after LSG in Chinese women.