scholarly journals Plasma Nitrate Levels Are Related to Metabolic Syndrome and Are Not Altered by Treatment with DPP-4 Inhibitor Linagliptin: A Randomised, Placebo-Controlled Trial in Patients with Early Type 2 Diabetes Mellitus

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1548
Author(s):  
Melanie Reijrink ◽  
Stefanie A. De De Boer ◽  
Anniek M. Van Van Roon ◽  
Riemer H. J. A. Slart ◽  
Bernadette O. Fernandez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Vegetable Intake ◽  
Early Type ◽  
Plasma Nitrate ◽  
Nitrate And Nitrite

The depletion of nitrate and nitrite, stable nitric oxide (NO) end-products, promotes adipose tissue dysfunction and insulin resistance (IR). Dipeptidyl peptidase-4 (DPP-4) inhibitors have the potentially beneficial side effect of increasing NO availability. In this study, nitrate and nitrite levels and the effects of DPP-4 inhibitor linagliptin were investigated in relation to metabolic syndrome (MetS) markers. Treatment-naive patients with early type 2 diabetes mellitus (T2DM) (n = 40, median age 63 IQR (55–67) years, 63% male, mean HbA1c 45 ± 4.4 mmol/mol) were randomized (1:1) to linagliptin (5 mg/day) or placebo. MetS-related markers (body mass index (BMI), triglycerides, HOMA-IR, gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and adiponectin), plasma levels of nitrate, nitrite, total free thiols (TFT) and vegetable intake were estimated at baseline and after 4 and 26 weeks of treatment. Plasma nitrate, but not nitrite, correlated positively with vegetable intake (r = 0.38, p = 0.018) and was inversely associated with HOMA-IR (r = −0.44, p = 0.006), BMI (r = −0.35, p = 0.028), GGT (r = −0.37, p = 0.019) and CRP (r = −0.34, p = 0.034). The relationship between nitrate and HOMA-IR remained significant after adjusting for BMI, CRP, vegetable intake and GGT. With stable vegetable intake, nitrate and nitrite, TFT, adipokines and CRP did not change after 26 weeks of linagliptin treatment. While plasma nitrate is inversely associated with MetS, linagliptin treatment does not significantly influence nitrate and nitrite concentrations, oxidative stress, adipose tissue function and systemic inflammation.

Brown Adipose Tissue, Thermogenesis, and Obesity: A Review of Literature

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Naglaa Raafat AbdRaboh ◽  
Aeman M. Asif ◽  
Sumbal Riaz ◽  
Hafez A. Ahmed
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Brown Adipose Tissue ◽  
Atp Synthesis ◽  
Brown Adipose

The white adipose tissue (WAT) mass in adult humans ranges between 10-35 kg. The cells are normally sensitive to insulin in the fed state, and to glucagon and adrenaline in fasting or during exercise. Well-fed sedentary individuals are prone to weight gain as they fall victims to the anabolic mechanisms led mainly by insulin. Brown adipose tissue (BAT), by contrast, stores smaller amounts of triglycerides in multi-locular droplets, is highly vascularized and its cells are rich in unique mitochondria which are capable of uncoupling oxidation from phosphorylation or ATP formation. The tissue is innerved by the sympathetic nervous system and is highly sensitive to iodothyronines. It releases heat in the body in response to sympathetic activity. BAT unique mitochondria express numerous cristae and, unlike ordinary mitochondria on other body cells including WAT cells, they express uncoupling protein-1 (UCP-1, or thermogenin). UCP-1 allows the mitochondria to oxidize more fat and glucose as they escape the controlling mechanisms that depend on the coupling of oxidation to the demand for ATP, i.e., uncouples oxidative phosphorylation. Thermogenin (UCP-1) is a natural un-coupler of oxidative phosphorylation as it dissipates the proton gradient generated across the inner mitochondrial membrane, which is required to attain a certain level for the activation of ATP synthesis in mitochondrial matrix. In BAT, ATP synthesis is inhibited, as the protons are dissipated, and most energy is released as heat. The different proportions and activity of BAT and WAT in different individuals might explain why some people are more prone to weight gain, and find it difficult to lose weight, than others; and also explains the tendency for weight gain as individuals get older. New approaches in the battle against obesity, metabolic syndrome and type 2 diabetes mellitus are expected through better understanding of how this balance between WAT and BAT is controlled. Interestingly, long term adrenergic stimulation of WAT induces browning of some white adipocytes, and the tissue gradually turns into & quot; beige & quot; adipose tissue, which shares characteristics of brown adipose tissue like thermogenesis, larger number of mitochondria and smaller lipid droplets, all developing in a gradual way. The adipose tissue interconverts its cell types in order to adapt for the changing metabolic balance and other stimuli. This phenomenon is currently incompletely understood, albeit significant for our understanding of obesity, metabolic syndrome and type 2 diabetes mellitus and many consequent complications of insulin resistance. Moreover, the nervous system is involved in the regulation of WAT and BAT through effects on fat cell proliferation, differentiation, trans-differentiation and apoptosis. The brain interacts with different adipocytes and adipokines in the pathogenesis of obesity, type 2 diabetes mellitus, anorexia, cachexia and other syndromes. This review will target many of these aspects in an attempt to draw more attention in the direction of this major health issue.

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