Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats trying to elucidate the underlying mechanisms. Animals were assigned into control rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric measures and biochemical analyses were performed to assess metabolic and liver function changes. The inflammatory and oxidative stress markers and the histopathology of rat liver tissues were also investigated. Groups with T2DM showed increased body weight, serum glucose, and insulin resistance. They exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and deterioration of liver function. Fasudil administration reduced body weight, insulin resistance, and raised liver enzymes. It improved the disturbed lipid profile and attenuated liver inflammation. Moreover, it slowed down the progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 expression. The present study demonstrated beneficial amelioration effect of fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving mitochondrial architecture, and inhibiting apoptosis.

• MeSH
• Diabetes Mellitus, Type 2 * complications   drug therapy   MeSH
• Diet, High-Fat adverse effects   MeSH
• Diabetes Mellitus, Experimental * complications   drug therapy   metabolism   MeSH
• Insulin Resistance * MeSH
• Liver metabolism   MeSH
• rho-Associated Kinases metabolism   MeSH
• Rats MeSH
• Lipids MeSH
• Non-alcoholic Fatty Liver Disease * drug therapy   pathology   MeSH
• Body Weight MeSH
• Inflammation metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• fasudil MeSH Browser
• rho-Associated Kinases MeSH
• Lipids MeSH

A substantial body of literature has provided evidence that type 2 diabetes mellitus (T2DM) and colorectal neoplasia share several common factors. Both diseases are among the leading causes of death worldwide and have an increasing incidence. In addition to usual risk factors such as sedentary lifestyle, obesity, and family history, common pathophysiological mechanisms involved in the development of these diseases have been identified. These include changes in glucose metabolism associated with adipose tissue dysfunction including insulin resistance resulting to hyperinsulinemia and chronic hyperglycemia. In addition to altered glucose metabolism, abdominal obesity has been associated with accented carcinogenesis with chronic subclinical inflammation. An increasing number of studies have recently described the role of the gut microbiota in metabolic diseases including T2DM and the development of colorectal cancer (CRC). Due to the interconnectedness of different pathophysiological processes, it is not entirely clear which factor is crucial in the development of carcinogenesis in patients with T2DM. The aim of this work is to review the current knowledge on the pathophysiological mechanisms of colorectal neoplasia development in individuals with T2DM. Here, we review the potential pathophysiological processes involved in the onset and progression of colorectal neoplasia in patients with T2DM. Uncovering common pathophysiological characteristics is essential for understanding the nature of these diseases and may lead to effective treatment and prevention.

• MeSH
• Adiposity MeSH
• Diabetes Mellitus, Type 2 epidemiology   microbiology   physiopathology   MeSH
• Dysbiosis MeSH
• Energy Metabolism MeSH
• Risk Assessment MeSH
• Hyperglycemia epidemiology   physiopathology   MeSH
• Hyperinsulinism epidemiology   physiopathology   MeSH
• Incidence MeSH
• Insulin Resistance MeSH
• Colorectal Neoplasms epidemiology   microbiology   physiopathology   MeSH
• Humans MeSH
• Obesity epidemiology   physiopathology   MeSH
• Risk Factors MeSH
• Gastrointestinal Microbiome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

• Keywords
• cardiac surgery, coronary artery disease, diabetes mellitus, endoplasmic reticulum stress, epicardial fat, gene expression, inflammation, mitochondrial dysfunction,
• MeSH
• Endoplasmic Reticulum genetics   metabolism   MeSH
• Gene Expression genetics   MeSH
• Muscle, Skeletal metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger genetics   MeSH
• Mitochondria genetics   metabolism   MeSH
• Myocardium metabolism   MeSH
• Coronary Artery Disease genetics   physiopathology   MeSH
• Pericardium metabolism   MeSH
• Subcutaneous Fat metabolism   MeSH
• Aged MeSH
• Gene Expression Profiling methods   MeSH
• Endoplasmic Reticulum Stress genetics   physiology   MeSH
• Transcriptome genetics   MeSH
• Adipose Tissue metabolism   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• RNA, Messenger MeSH

PURPOSE: Cushing's syndrome is characterized by metabolic disturbances including insulin resistance. Mitochondrial dysfunction is one pathogenic factor in the development of insulin resistance in patients with obesity. We explored whether mitochondrial dysfunction correlates with insulin resistance and other metabolic complications. PATIENTS AND METHODS: We investigated the changes of mRNA expression of genes encoding selected subunits of oxidative phosphorylation system (OXPHOS), pyruvate dehydrogenase (PDH) and citrate synthase (CS) in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) and mitochondrial enzyme activity in platelets of 24 patients with active Cushing's syndrome and in 9 of them after successful treatment and 22 healthy control subjects. RESULTS: Patients with active Cushing's syndrome had significantly increased body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and serum lipids relative to the control group. The expression of all investigated genes for selected mitochondrial proteins was decreased in SCAT in patients with active Cushing's syndrome and remained decreased after successful treatment. The expression of most tested genes in SCAT correlated inversely with BMI and HOMA-IR. The expression of genes encoding selected OXPHOS subunits and CS was increased in PM in patients with active Cushing's syndrome with a tendency to decrease toward normal levels after cure. Patients with active Cushing's syndrome showed increased enzyme activity of complex I (NQR) in platelets. CONCLUSION: Mitochondrial function in SCAT in patients with Cushing's syndrome is impaired and only slightly affected by its treatment which may reflect ongoing metabolic disturbances even after successful treatment of Cushing's syndrome.

• Keywords
• Cushing’s syndrome, gene expression, insulin resistance, mitochondrial enzyme activity,
• Publication type
• Journal Article MeSH