Research Progress on the Mechanisms of the Effects of Laparoscopic Sleeve Gastrectomy on Free Fatty Acids and Tumor Necrosis Factor in Obese Patients

  • Na Liu Department of Endocrinology, the First People’s Hospital of Kunming, Kunming 650000, Yunnan, China
  • Xiaolei Chen Department of Endocrinology, the First People’s Hospital of Kunming, Kunming 650000, Yunnan, China
  • Na Yao Department of Endocrinology, the First People’s Hospital of Kunming, Kunming 650000, Yunnan, China
  • Haibin Wang Department of Infectious Diseases, Affiliated Hospital of Yunnan University, Kunming 650000, Yunnan, China
  • Ya He Department of Endocrinology, the First People’s Hospital of Kunming, Kunming 650000, Yunnan, China
  • Jiali Zhou Department of Endocrinology, the First People’s Hospital of Kunming, Kunming 650000, Yunnan, China
  • Quanmei Li Department of Endocrinology, the First People’s Hospital of Kunming, Kunming 650000, Yunnan, China
  • Meng Han Department of Endocrinology, the First People’s Hospital of Kunming, Kunming 650000, Yunnan, China
Keywords: Laparoscopic sleeve gastrectomy, Free fatty acids, Tumor necrosis factor, Obesity, Metabolic syndrome

Abstract

Laparoscopic sleeve gastrectomy (LSG), as an effective treatment for morbid obesity and its metabolic complications, exerts its therapeutic effects by significantly reducing body weight and improving metabolic disorders. Its core mechanisms involve multi-level regulation of free fatty acid (FFA) metabolism and chronic low-grade inflammatory states (represented by tumor necrosis factor-alpha, TNF-α). This paper systematically reviews the direct impact of LSG on FFA dynamics (including lipolysis, tissue uptake, and oxidation), as well as the molecular pathways through which it indirectly regulates TNF-α by reducing adipose tissue inflammation, improving intestinal barrier function, and modulating epigenetic modifications (such as SCD gene methylation). Postoperatively, FFA and TNF-α form a bidirectional promoting feedback loop. LSG effectively breaks this vicious cycle of mutual promotion between the two under obese conditions by reducing FFA levels and inhibiting TNF-α expression. Lower FFA levels alleviate inflammatory signal activation, while reduced TNF-α inhibits lipolysis, collectively promoting the restoration of insulin sensitivity. A thorough understanding of these mechanisms provides a theoretical basis for optimizing surgical strategies and developing targeted therapies.

References

Rubino F, Forgione A, Cummings D, et al., 2006. The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes. Annals of Surgery, 244: 741–749.

Rubino F, Gagner M, Gentileschi P, et al., 2004. The Early Effect of the Roux-en-Y Gastric Bypass on Hormones Involved in Body Weight Regulation and Glucose Metabolism. Annals of Surgery, 240: 236–242.

Langer F, Reza Hoda M, Bohdjalian A, et al., 2005. Sleeve Gastrectomy and Gastric Banding: Effects on Plasma Ghrelin Levels. Obesity Surgery, 15(7): 1024–1029.

Thaler J, Cummings D, 2009. Minireview: Hormonal and Metabolic Mechanisms of Diabetes Remission After Gastrointestinal Surgery. Endocrinology, 150: 2518–2525.

Le Roux C, Aylwin S, Batterham R, et al., 2006. Gut Hormone Profiles Following Bariatric Surgery Favor an Anorectic State, Facilitate Weight Loss, and Improve Metabolic Parameters. Annals of Surgery, 243: 108–114.

Shin A, Berthoud H, 2013. Obesity Surgery: Happy With Less or Eternally Hungry? Trends in Endocrinology and Metabolism, 24(2): 101–108.

Campos G, Rabl C, Havel P, et al., 2014. Changes in Post-Prandial Glucose and Pancreatic Hormones, and Steady-State Insulin and Free Fatty Acids After Gastric Bypass Surgery. Surgery for Obesity and Related Diseases, 10(1), 1–8.

Farey J, Preda T, Fisher O, et al., 2017. Effect of Laparoscopic Sleeve Gastrectomy on Fasting Gastrointestinal, Pancreatic, and Adipose-Derived Hormones and on Non-Esterified Fatty Acids. Obesity Surgery, 27(2), 399–407.

Morcillo S, Martín-Núñez G, García-Serrano S, et al., 2017. Changes in SCD Gene DNA Methylation After Bariatric Surgery in Morbidly Obese Patients Are Associated with Free Fatty Acids. Scientific Reports, 7(1), 46292.

Wrzosek M, Zawadzka Z, Sawicka A, et al., 2022. Impact of Fatty Acids on Obesity-Associated Diseases and Radical Weight Reduction. Obesity Surgery, 32(2), 428–440.

Gu N, Guo Q, Mao K, et al., 2015. Palmitate Enhances Musclin Gene Expression by Activating the PERK Signaling Pathway in C2C12 Myotubes. Biochemical and Biophysical Research Communications, 467.

Agrawal S, Gollapudi S, Su H, 2011. Leptin Activates Human B Cells to Secrete TNF-α, IL-6, and IL-10 Through the JAK2/STAT3 and p38MAPK/ERK1/2 Signaling Pathways. Journal of Clinical Immunology, 31.

Ion R, Hutanu A, Sala D, et al., 2024. Short-Term Changes in TNF-α, IL-6, and Adiponectin Levels Following Bariatric Surgery in Caucasian Obese Adults: An Observational Case-Control Study. Medicina (Lithuania), 60(11), 1789.

Maymó-Masip E, Fernández-Veledo S, Garcia España A, et al., 2013. The Rise of Soluble TWEAK Levels in Severly Obese Subjects after Bariatic Surgery May Affect Adipocyte-Cytokine Production Induced by TNF-α. Journal of Clinical Endocrinology and Metabolism, 98(8), 1323–1333.

Tabasi M, Ashrafian F, Khezerloo J, et al., 2019. Alterations in Gut Microbiota and Hormones Post-Bariatric Surgery: A Comprehensive Review from Bench to Bedside. Obesity Surgery, 29(5): 1663–1674.

Koliada A, Syzenko G, Moseiko V, et al., 2017. Correlation Between Body Mass Index and Firmicutes/Bacteroidetes Ratio in an Adult Ukrainian Population. BMC Microbiology, 17(1): 1–6.

Graessler J, Qin Y, Zhong H, et al., 2013. Metagenomic Analysis of the Human Gut Microbiome in Obese Patients with Type 2 Diabetes Before and After Bariatric Surgery: Association with Inflammatory and Metabolic Markers. The Pharmacogenomics Journal, 13(6): 514–522.

Anhê F, Varin T, Schertzer J, et al., 2017. The Gut Microbiota as a Mediator of the Metabolic Benefits Following Bariatric Surgery. Canadian Journal of Diabetes, 41(4): 439–447.

Tabasi M, Eybpoosh S, Siadat S, et al., 2021. Modulation of the Gut Microbiota and Serum Biomarkers After Laparoscopic Sleeve Gastrectomy: A 1-Year Follow-Up Study. Obesity Surgery, 31(5), 1949–1956.

Kim K, Choi S, Zhou Y, et al., 2017. The Hepatic FXR/SHP Axis Modulates Systemic Glucose and Fatty Acid Homeostasis in Aged Mice. Hepatology, 66(2), 498–509.

Ding L, Fang Z, Liu Y, et al., 2019. Targeting Bile Acid-Activated Receptors in Bariatric Surgery. Bile Acids and Their Receptors, 256: 359–378.

Albaugh V, Banan B, Antoun J, et al., 2019. The Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery. Gastroenterology, 156(4), 1041–1051.

Wang C, Ha X, Li W, et al., 2017. Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity. Inflammation, 40(1), 42–51.

Volpe C, Nogueira-Machado J, 2013. The Dual Role of Free Fatty Acid Signaling in Inflammation and Therapeutics. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 7(3), 189–197.

Ahmad R, Al-Roub A, Kochumon S, et al., 2018. The Synergy Between Palmitate and TNF-α for CCL2 Production Is Dependent on the TRIF/IRF3 Pathway: Implications for Metabolic Inflammation. Journal of Immunology, 200(10), 3599–3611.

Feldstein A, Werneburg N, Canbay A, et al., 2004. Free Fatty Acids Promote Hepatic Lipotoxicity by Stimulating TNF-α Expression via a Lysosomal Pathway. Hepatology, 40(1), 185–194.

Rui L, Aguirre V, Kim J, et al., 2001. Insulin/IGF-1 and TNF-α Stimulate Phosphorylation of IRS-1 at Inhibitory Ser307 via Distinct Pathways. Journal of Clinical Investigation, 107(2), 181–189.

Nguyen M, Satoh H, Favelyukis S, et al., 2005. JNK and Tumor Necrosis Factor-Alpha Are Mediators of Free Fatty Acid-Induced Insulin Resistance in 3T3-L1 Adipocytes. Journal of Biological Chemistry, 280(42), 35361–35371.

Published
2025-10-17