Evidence That Peripheral Leptin Resistance in Omental Adipose Tissue and Liver Correlates with MASLD in Humans

• Published in: International journal of molecular sciences Vol. 25; no. 12; p. 6420
• Main Authors: De la Cruz-Color, Lucia, Dominguez-Rosales, Jose Alfredo, Maldonado-González, Montserrat, Ruíz-Madrigal, Bertha, Sánchez Muñoz, Martha P, Zaragoza-Guerra, Vianney Alejandrina, Espinoza-Padilla, Victor H, Ruelas-Cinco, Elizabeth Del C, Ramírez-Meza, Sandra M, Torres Baranda, José R, González-Gutiérrez, María Del R, Hernandez Nazara, Zamira Helena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-06-2024; MDPI
• Subjects: Adipocytes; Adipose Tissue - metabolism; Adipose tissues; Adult; Amino acids; Analysis; Biopsy; Body fat; Body mass index; Enzymes; Fatty Liver - metabolism; Fatty Liver - pathology; Female; Health aspects; Humans; Insulin Resistance; Leptin; Leptin - metabolism; leptin receptor; Liver; Liver - metabolism; Male; Middle Aged; Obesity; Obesity in children; Omentum - metabolism; Omentum - pathology; Overweight; patatin-like phospholipase domain-containing protein 2; Protein expression; Proteins; Receptors, Leptin - genetics; Receptors, Leptin - metabolism; Risk factors; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; stearoyl-coa desaturase-1; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; sterol regulatory element-binding transcription factor 1; suppressor of cytokine signaling 3; Suppressor of Cytokine Signaling 3 Protein - genetics; Suppressor of Cytokine Signaling 3 Protein - metabolism; Type 2 diabetes; Mexico; suppressor of cytokine signaling 3; non-alcoholic fatty liver disease; patatin-like phospholipase domain-containing protein 2; stearoyl-coa desaturase-1; leptin receptor; sterol regulatory element-binding transcription factor 1; leptin; metabolic dysfunction-associated steatohepatitis; metabolic dysfunction-associated steatotic liver disease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25126420

Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (
), suppressor of cytokine signaling 3 (
), sterol regulatory element-binding transcription factor 1 (
), stearoyl-CoA desaturase-1 (
), and patatin-like phospholipase domain-containing protein 2 (
), were determined from liver and adipose tissue. Higher serum leptin and
levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver,
was positively correlated with leptin expression in adipose tissue, and
was correlated with
. In OAT,
was correlated with insulin resistance and transaminase enzymes (
< 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.