Search Results (5)

Background/Objectives: Obesity is a major public health concern that increases the risk of chronic diseases. In obesity, adipose tissue undergoes remodeling, which is associated with chronic low-grade inflammation and disruption of its homeostatic mechanisms including endoplasmic reticulum (ER) function and autophagy. Fish oil (FO) and tart cherry (TC) have known anti-inflammatory properties. We hypothesized that while TC and FO individually decrease inflammation, their combined effects will be greater and will be either synergistic or additive in regulating inflammation and other adipose tissue functions. Methods: Here, we conducted gene expression analyses, using qRT-PCR, on gonadal white adipose tissues from a previous study where male and female C57BL/6J (B6) and TALLYHO/Jng (TH) mice were fed low fat (LF), high fat (HF), or HF diets supplemented with TC, FO, or TC + FO for 14 weeks from weaning. Data was statistically analyzed by one or two-way ANOVA, using GraphPad Prism. Results: HF diet increased adiposity and upregulated markers of inflammation, ER stress, and autophagy compared to the LF diet in both mouse models. While both TC and FO supplementation individually reduced the expression of inflammatory, ER stress, and autophagy markers on HF diet, their combination showed no consistent additive or synergistic effects. Conclusions: Overall, our findings suggest that although TC and FO effectively mitigate inflammation in white adipose tissue, their combined use did not result in synergistic or additive effects of the two interventions. Full article

Lower urinary tract symptoms are extremely common in people with diabetes and obesity, but the causes are unclear. Furthermore, it has proven difficult to reliably demonstrate bladder dysfunction in diabetic mouse models, thus limiting the ability to gain mechanistic insights. Therefore, the main objective of this experimental study was to characterize diabetic bladder dysfunction in three promising polygenic mouse models of type 2 diabetes. We performed periodic assessments of glucose tolerance and micturition (void spot assay) for eight to twelve months. Males and females and high-fat diets were tested. NONcNZO10/LtJ mice did not develop bladder dysfunction over twelve months. TALLYHO/JngJ males were severely hyperglycemic from two months of age (fasted blood glucose ~550 mg/dL), while females were moderately so. Although males exhibited polyuria, neither they nor the females exhibited bladder dysfunction over nine months. KK.Cg-A^y/J males and females were extremely glucose intolerant. Males exhibited polyuria, a significant increase in voiding frequency at four months (compensation), followed by a rapid drop in voiding frequency by six months (decompensation) which was accompanied by a dramatic increase in urine leakage, indicating loss of outlet control. At eight months, male bladders were dilated. Females also developed polyuria but compensated with larger voids. We conclude KK.Cg-A^y/J male mice recapitulate key symptoms noted in patients and are the best model of the three to study diabetic bladder dysfunction. Full article

Diabetes incidence is rising globally at an accelerating rate causing issues at both the individual and societal levels. However, partly inspired by Ayurvedic medicine, a naturally occurring compound called pterostilbene has been demonstrated to protect against diabetes symptoms, though mainly in rats. The purpose of this study was to investigate the putative protective effect of pterostilbene on the two main aspects of diabetes, namely insulin resistance and decreased insulin secretion, in mice. To accomplish this, we employed diet-induced obese as well as streptozotocin-induced diabetic C57BL/6NTac mice for fasting glucose homeostasis assessment, tolerance tests and pancreas perfusions. In addition, we used the polygenic model of diabetes TALLYHO/JngJ to assess for prevention of β-cell burnout. We found that the diet-induced obese C57BL/6NTac mice were insulin resistant, but that pterostilbene had no impact on this or on overall glucose regulation. We further found that the reported protective effect of pterostilbene against streptozotocin-induced diabetes was absent in C57BL/6NTac mice, despite a promising pilot experiment. Lastly, we observed that pterostilbene does not prevent or delay onset of β-cell burnout in TALLYHO/JngJ mice. In conjunction with the literature, our findings suggest variations in the response to pterostilbene between species or between strains of species. Full article

Critical limb ischemia (CLI) is a severe complication of diabetes mellitus that occurs without effective therapy. Excessive reactive oxygen species (ROS) production and oxidative stress play critical roles in the development of diabetic cardiovascular complications. N-acetylcysteine (NAC) reduces ischemia-induced ROS production. The present study aimed to investigate the effect of NAC on the recovery of ischemic limb in an experimental model of type-2 diabetes. TALLYHO/JngJ diabetic and SWR/J non-diabetic mice were used for developing a CLI model. For NAC treatment, mice received NAC (1 mg/mL) in their drinking water for 24 h before initiating CLI, and continuously for the duration of the experiment. Blood flow, mechanical function, histology, expression of antioxidant enzymes including superoxide dismutase (SOD)-1, SOD-3, glutathione peroxidase (Gpx)-1, catalase, and phosphorylated insulin receptor substrate (IRS)-1, Akt, and eNOS in ischemic limb were evaluated in vivo or ex vivo. Body weight, blood glucose, plasma advanced glycation end-products (AGEs), plasma insulin, insulin resistance index, and plasma TNF-a were also evaluated during the experiment. NAC treatment effectively attenuated ROS production with preserved expressions of SOD-1, Gpx-1, catalase, phosphorylated Akt, and eNOS, and enhanced the recovery of blood flow and function of the diabetic ischemic limb. NAC treatment also significantly decreased the levels of phosphorylated IRS-1 (Ser307) expression and plasma TNF-α in diabetic mice without significant changes in blood glucose and AGEs levels. In conclusion, NAC treatment enhanced the recovery of blood flow and mechanical function in ischemic limbs in T2D mice in association with improved tissue redox/inflammatory status and insulin resistance. Full article

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na⁺ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na⁺ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na⁺ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice. Full article