Restricted accessResearch articleFirst published online 2025-09
Heat Shock Protein β2 is Associated with the Weight-Loss Outcome 1 Year after Laparoscopic Sleeve Gastrectomy in Patients with Body Mass Index ≥32.5 kg/m 2
Tandem mass tag (TMT) labeling technology in labeled quantitative proteomics has been widely used in studying differentially expressed proteins (DEPs).
Objectives:
The purpose of the research was to explore DEPs closely associated with optimal initial clinical response.
Methods:
Optimal initial clinical response was defined as a percentage of excess weight loss (%EWL) ≥50%. Using TMT technology and bioinformatics, we screened DEPs to identify those associated with weight-loss outcomes 1 year after surgery. Key DEPs were validated using western blotting and immunohistochemistry in tissue samples from patients with optimal and suboptimal clinical responses.
Results:
We enrolled 26 patients, including 13 with optimal initial clinical response and 13 with suboptimal initial clinical response. Of the 267 DEPs screened, only heat shock protein β2 (HSPβ2) best evaluated the weight loss, with an optimal cutoff of 0.8206 (area under the curve, 1.000; 95% confidence interval: 0.868–1.000; sensitivity, 100.00%; specificity, 100.00%). In an external validation cohort, the HSPβ2 expression was significantly lower in the optimal initial clinical response group than in the suboptimal initial clinical response group.
Conclusions:
HSPβ2 is closely associated with the weight-loss outcome of laparoscopic sleeve gastrectomy.
Get full access to this article
View all access options for this article.
References
1.
JensenMD, RyanDH, ApovianCM, et al.2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation, 2014; 129129(25 Suppl 2):S102–S38.
2.
MisraS, BhattacharyaS, Saravana KumarS, et al.Long-term outcomes of laparoscopic sleeve gastrectomy from the Indian subcontinent. Obes Surg, 2019; 29(12):4043–4055.
3.
PeterliR, WölnerhanssenBK, PetersT, et al.Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss in patients with morbid obesity: The SM-BOSS randomized clinical trial. JAMA, 2018; 319(3):255–265.
4.
YangJ, WangC, CaoG, et al.Long-term effects of laparoscopic sleeve gastrectomy versus roux-en-Y gastric bypass for the treatment of Chinese type 2 diabetes mellitus patients with body mass index 28-35 kg/m(2). BMC Surg, 2015; 15:88.
5.
AngrisaniL, SantonicolaA, IovinoP, et al.Bariatric surgery worldwide 2013. Obes Surg, 2015; 25(10):1822–1832.
6.
KhorgamiZ, ShoarS, AndalibA, et al.Trends in utilization of bariatric surgery, 2010-2014: Sleeve gastrectomy dominates. Surg Obes Relat Dis, 2017; 13(5):774–778.
7.
LomantoD, LeeWJ, GoelR, et al.Bariatric surgery in Asia in the last 5 years (2005-2009). Obes Surg, 2012; 2222(3):502–506.
8.
BiolettoF, PellegriniM, D’EusebioC, et al.Development and validation of a scoring system for pre-surgical and early post-surgical prediction of bariatric surgery unsuccess at 2 years. Sci Rep, 2021; 11(1):21067.
9.
Carvalho SilveiraF, MarangaG, MitchellF, et al.First-year weight loss following gastric band surgery predicts long-term outcomes. ANZ J Surg, 2021; 91(11):2443–2446.
10.
CiudinA, FidilioE, Gutiérrez-CarrasquillaL, et al.A clinical-genetic score for predicting weight loss after bariatric surgery: The OBEGEN study. J Pers Med, 2021; 1111(10).
11.
LiuF, HeJ, ZhuY, et al.Body adiposity index is predictive of weight loss after Roux-en-Y gastric bypass. Ann Nutr Metab, 2021; 77(3):168–177.
12.
MarekRJ, WilliamsGA, MohunSH, et al.Surgery type and psychosocial factors contribute to poorer weight loss outcomes in persons with a body mass index greater than 60 kg/m(2). Surg Obes Relat Dis, 2017; 13(12):2021–2026.
13.
Martin-FernandezKW, CreelDB, SchuhLM. Psychosocial and behavioral correlates of weight loss 12 to 15 years after bariatric surgery. J Behav Med, 2022; 45(2):252–259.
14.
WangL, XuG, TianC, et al.Combination of single-nucleotide polymorphisms and preoperative body mass index to predict weight loss after Laproscopic sleeve gastrectomy in chinese patients with body mass index ≥ 32.5 kg/m(2). Obes Surg, 2022; 32(12):3951–3960.
15.
BrandacherG, GoldererG, KienzlK, et al.Potential applications of global protein expression analysis (proteomics) in morbid obesity and bariatric surgery. Obes Surg, 2008; 18(7):905–910.
16.
CarruthersNJ, Strieder-BarbozaC, CarusoJA, et al.The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity. Sci Rep, 2021; 11(1):17394.
17.
Varela-RodríguezBM, Juiz-ValiñaP, VarelaL, et al.Beneficial effects of bariatric surgery-induced by weight loss on the proteome of abdominal subcutaneous adipose tissue. J Clin Med, 2020; 99(1).
18.
RossPL, HuangYN, MarcheseJN, et al.Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics, 2004; 3(12):1154–1169.
19.
WangS, ZhangY, HuS, et al.AGDMP1 alleviates insulin resistance by modulating heat shock protein 60-mediated IRS-1/AKT/GLUT4 pathway and adipose inflammation: A potential therapeutic peptide for gestational diabetes mellitus. Faseb J, 2025; 39(2):e70339.
20.
SchroederHT, De Lemos MullerCH, HeckTG, et al.Resolution of inflammation in chronic disease via restoration of the heat shock response (HSR). Cell Stress Chaperones, 2024; 29(1):66–87.
21.
ArcherAE, Von SchulzeAT, GeigerPC. Exercise, heat shock proteins and insulin resistance. Philos Trans R Soc Lond B Biol Sci, 2018; 373(1738):20160529.
22.
DuD, WangL, ChenW, et al.Weight loss at six months is the surrogate of long-term treatment outcomes for obese Chinese with a BMI less than 35 kg/m(2) undergoing Roux-en-Y gastric bypass. Asian J Surg, 2022; 45(9):1682–1687.
23.
WangL, SangQ, DuD, et al.Early weight loss after laparoscopic sleeve gastrectomy predicts sustained weight maintenance among Chinese individuals with a BMI < 35 kg/m(2). Obes Surg, 2021; 3131(4):1647–1655.
24.
WangL, SangQ, ZhengX, et al.Early weight loss following laparoscopic sleeve gastrectomy is predictive of long-term weight loss in morbidly obese Chinese. Obes Surg, 2021; 31(2):820–828.
25.
SuzukiA, SugiyamaY, HayashiY, et al.MKBP, a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase. J Cell Biol, 1998; 140(5):1113–1124.
26.
OshitaSE, ChenF, KwanT, et al.The small heat shock protein HspB2 is a novel anti-apoptotic protein that inhibits apical caspase activation in the extrinsic apoptotic pathway. Breast Cancer Res Treat, 2010; 124(2):307–315.
27.
PrabhuS, RamanB, RamakrishnaT, et al.HspB2/myotonic dystrophy protein kinase binding protein (MKBP) as a novel molecular chaperone: Structural and functional aspects. PLoS One, 2012; 7(1):e29810.
28.
YoshidaK, AkiT, HaradaK, et al.Translocation of HSP27 and MKBP in ischemic heart. Cell Struct Funct, 1999; 24(4):181–185.
29.
GolenhofenN, PerngMD, QuinlanRA, et al.Comparison of the small heat shock proteins alphaB-crystallin, MKBP, HSP25, HSP20, and cvHSP in heart and skeletal muscle. Histochem Cell Biol, 2004; 122(5):415–425.
30.
HuZ, YangB, LuW, et al.HSPB2/MKBP, a novel and unique member of the small heat-shock protein family. J Neurosci Res, 2008; 86(10):2125–2133.
31.
van der KolkBW, MuniandyM, KaminskaD, et al.Differential mitochondrial gene expression in adipose tissue following weight loss induced by diet or bariatric surgery. J Clin Endocrinol Metab, 2021; 106(5):1312–1324.
32.
ChewCAZ, TanIJ, NgHJH, et al.Early weight loss after laparoscopic sleeve gastrectomy predicts midterm weight loss in morbidly obese Asians. Surg Obes Relat Dis, 2017; 13(12):1966–1972.
