BDNF x adiponectin

Brain‐derived neurotrophic factor (BDNF) is expressed in the white adipose tissues (WATs), and the expression increases during high‐fat diet (HFD) feeding, implicating its role in obesity. Here, we focused on BDNF expression in epididymal WAT (eWAT), a visceral adipose tissue, in mice. During 2 weeks of HFD feeding, Bdnf mRNA expression in eWAT slightly increased, but a robust increase was observed after 8 weeks of HFD feeding. This upregulation of Bdnf mRNA was correlated with significant induction of hypoxia‐inducible factor 1α (Hif1α) and platelet‐derived growth factor subunit B (Pdgfb) mRNA in eWAT following 8 weeks of HFD feeding. Furthermore, the increased expression of the M1 macrophage markers was strongly correlated with the elevation of Bdnf mRNA in the eWAT. Notably, 8 weeks of HFD feeding significantly elevated Tnfα mRNA expression in eWAT, while no such induction was observed in inguinal WAT (iWAT). In contrast, the expression of Adipoq (adiponectin), implicated in improved insulin sensitivity and anti‐inflammatory effects, was significantly upregulated in iWAT, but not in eWAT. Thus, our study may show the role of BDNF in eWAT in obesity models, potentially contributing to the pathological state of visceral adipose tissues.

To define the impact of obesity on inflammatory and oxidative disturbances in antipsychotic‐treated schizophrenia patients.

Several cytokines, inflammatory, metabolic, and oxidative status markers were evaluated in obese (n = 40) and non‐obese (n = 40) antipsychotic‐treated patients and compared with age‐and BMI‐matched controls (n = 80).

Schizophrenia patients had higher leptin, TNF‐α, adiponectin, visfatin, resistin, P‐selectin, NPY, BDNF, CD40‐L, MCP‐1, and malondialdehyde, and lower IL‐6, ghrelin, neopterin, and vitamin E levels compared to their respective controls (p < 0.001). Total oxidant status was higher in non‐obese patients compared to controls (p < 0.001), total antioxidant capacity was higher in obese compared to non‐obese patients (p < 0.01), but vitamin A and paraoxonase levels were not different. High sensitive‐CRP levels were higher in obsese controls relative to non‐obese controls (p < 0.05) and in obese patients relative to non‐obese patients (p < 0.001). Fasting glucose, insulin, HbA1c, HOMA‐IR, uric acid, total cholesterol, and triglyceride concentrations were higher in obese patients compared to non‐obese patients. Insulin concentrations and HOMA‐IR were also higher in obese controls than in non‐obese controls.

Our results suggest that inflammatory responses and oxidative stress develop independently from obesity in antipsychotic‐treated schizophrenia patients. However, schizophrenia‐induced obesity causes metabolic disturbances; thereby, obese schizophrenia patients are more liable to cardiovascular events and progress of metabolic syndrome than non‐obese patients.

The comorbidity between diabetes mellitus and depression was revealed, and diabetes mellitus increased the prevalence of depressive disorder, which ranked 13th in the leading causes of disability‐adjusted life‐years. Insulin resistance, which is common in diabetes mellitus, has increased the risk of depressive symptoms in both humans and animals. However, the mechanisms behind the comorbidity are multi‐factorial and complicated. There is still no causal chain to explain the comorbidity exactly. Moreover, Selective serotonin reuptake inhibitors, insulin and metformin, which are recommended for treating diabetes mellitus‐induced depression, were found to be a risk factor in some complications of diabetes.

Given these problems, many researchers made remarkable efforts to analyze diabetes complicating depression from different aspects, including insulin resistance, stress and Hypothalamic–Pituitary–Adrenal axis, neurological system, oxidative stress, and inflammation. Drug therapy, such as Hydrogen Sulfide, Cannabidiol, Ascorbic Acid and Hesperidin, are conducive to alleviating diabetes mellitus and depression. Here, we reviewed the exact pathophysiology underlying the comorbidity between depressive disorder and diabetes mellitus and drug therapy.

The review refers to the available literature in PubMed and Web of Science, searching critical terms related to diabetes mellitus, depression and drug therapy.

In this review, we found that brain structure and function, neurogenesis, brain‐derived neurotrophic factor and glucose and lipid metabolism were involved in the pathophysiology of the comorbidity. Obesity might lead to diabetes mellitus and depression through reduced adiponectin and increased leptin and resistin. In addition, drug therapy displayed in this review could expand the region of potential therapy.

The review summarizes the mechanisms underlying the comorbidity. It also overviews drug therapy with anti‐diabetic and anti‐depressant effects.