Objective: Obesity, inflammation, and decreased neuropeptide Y (NPY) are risk factors for depression. Dipeptidyl peptidase-4 (DPP4), a newly identified adipokine, has been proved to promote inflammation and NPY degradation. Hence, we aimed to investigate the association between plasma DPP4 activity and depression symptoms in middle-aged and older adults.
Methods: We cross-sectionally assessed 1,335 Chinese adults aged 45-76 years recruited from the Medical Examination Center, Guilin, China, between 2013 and 2014. The main outcome measures were plasma DPP4 activity, inflammatory markers, and NPY. Depression symptoms were determined by the score on the 9-item Patient Health Questionnaire (PHQ-9). Each of the 9 depression items of the PHQ-9 correspond to 1 of the DSM-IV diagnostic criteria for symptoms of major depressive disorder.
Results: Subjects in the highest quartile of DPP4 activity had higher body mass index (BMI), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and PHQ-9 score compared with subjects in the lowest quartile (P < .05). Compared to patients without depression symptoms, patients with depression symptoms had higher BMI, waist-to-hip ratio, IL-6, hs-CRP, and DPP4 activity (P < .05). DPP4 activity was associated positively with IL-6, hs-CRP, and PHQ-9 score and negatively with NPY after adjustment for potential confounders (P < .05). The risk for depression symptoms increased with higher levels of DPP4 activity and inflammation and lower levels of NPY.
Conclusions: Increased DPP4 activity is independently associated with depression symptoms in middle-aged and older adults. The mechanisms might be partly explained by mutual influence among inflammation, NPY, and DPP4. These observations raise further interest in DPP4 activity for the potential effect on inflammation and NPY metabolism, as a risk biomarker, or even a possible therapeutic target for depression.
Trial Registration: Chinese Clinical Trial Registry (ChiCTR-EPC-14005273).
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http://dx.doi.org/10.4088/JCP.15m10154 | DOI Listing |
J Endocrinol
January 2025
N Inagaki, Department of Diabetes, Endocrinology and Nutrition, Kyoto University, Kyoto, Japan.
Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs) are widely used as antidiabetic and anti-obesity agents. Although conventional GLP-1 RAs such as liraglutide and semaglutide are acylated with fatty acids to delay their degradation by dipeptidylpeptidase-4 (DPP-4), the manufacturing process is challenging. We previously developed selectively lipidated GLP-1 peptides at their only tryptophan residue (peptide A having one 8-amino-3,6-dioxaoctanoic acid (miniPEG) linker and peptide B having three miniPEG linkers).
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
School of Pharmaceutical Sciences, Nanjing Tech University, 30 Puzhu South Road, Nanjing 211816, People's Republic of China. Electronic address:
Sepsis is a fatal organ dysfunction characterized by the simultaneous hyperinflammation and immunosuppression. Nowadays, the early precision intervention of sepsis is challenging. Ferroptosis is involved in the development of sepsis.
View Article and Find Full Text PDFClin Gastroenterol Hepatol
January 2025
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address:
Hepatocellular carcinoma (HCC) is a major concern for public health. Fatty liver disease, related to alcohol misuse or metabolic syndrome, has become the leading cause of chronic liver disease and HCC. The strong association between type 2 diabetes mellitus and HCC can be partly attributed to the development of metabolic dysfunction associated steatotic liver disease (MASLD).
View Article and Find Full Text PDFDiabetes Care
January 2025
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada.
Objective: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, separately, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with a reduced risk of cirrhosis and other adverse liver outcomes among patients with type 2 diabetes.
Research Design And Methods: With an active comparator, new-user approach, we conducted a cohort study using the U.K.
bioRxiv
December 2024
Laboratorio de Genética e Cardiologia Molecular, Faculdade de Medicina, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Dipeptidyl peptidase 4 (DPP4) is a transmembrane serine exopeptidase abundantly expressed in the kidneys, predominantly in the proximal tubule (PT); however, its non-enzymatic functions in this nephron segment remain poorly understood. While DPP4 physically associates with the Na/H exchanger isoform 3 (NHE3) and its inhibitors exert natriuretic effects, the DPP4 role in blood pressure (BP) regulation remains controversial. This study investigated the effects of PT-specific deletion ( ) and global deletion ( ) on systolic blood pressure (SBP), natriuresis, and NHE3 regulation under baseline and angiotensin II (Ang II)-stimulated conditions in both male and female mice.
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