In contrast to Western diet, a plant‐based, high‐fat, low‐sugar diet does not exacerbate retinal endothelial injury in streptozotocin‐induced diabetes

Abstract

Controversy remains about how diet affects the vascular endothelial dysfunction associated with disordered insulin‐glucose homeostasis. It is postulated that the type and level of certain macronutrients contribute to endothelial dysfunction in vascular diabetes complications. However, it is not well understood how specific macronutrients affect the molecular inflammatory response under conditions of hyperglycemia. Here, we examined retinal microvascular endothelial injury in streptozotocin (STZ)‐diabetic rats fed a laboratory Western diet (WD). WD, characterized by its high content of saturated fat, cholesterol, and sugar, significantly increased retinal leukocyte accumulation and endothelial injury in the STZ‐diabetic rats. Suppression of endothelial NF‐κB signaling in the STZ model reduced the WD‐induced increase in leukocyte accumulation. To isolate the effect of dietary fat, we generated high‐fat diets with varying fatty acid balance and type. These diets contained moderate amounts of carbohydrates but no sugar. We found that neither high levels of saturated or unsaturated fats per se increased retinal leukocyte accumulation and endothelial injury in the STZ‐diabetic rat model but that the combination of high levels of dietary cholesterol with specific saturated fatty acids that are abundant in WD exacerbated leukocyte accumulation and endothelial injury in the retinas of STZ‐diabetic rats.—Barakat, A., Nakao, S., Zandi, S., Sun, D., Schmidt‐Ullrich, R., Hayes, K. C., Hafezi‐Moghadam, A. In contrast to Western diet, a plant‐based, high‐fat, low‐sugar diet does not exacerbate retinal endothelial injury in streptozotocin‐induced diabetes. FASEB J. 33, 10327–10338 (2019). http://www.fasebj.org

Deletion of Thioredoxin-Interacting Protein (TXNIP) Abrogates High Fat Diet-Induced Retinal Leukostasis, Barrier Dysfunction and Microvascular Degeneration in a Mouse Obesity Model

“…In agreement, our results showed that HFD-induced leukostasis after 8 weeks was positively correlated with development of acellular capillaries and decreased vascular density after 18 weeks in WT-HFD, but not in TKO mice. Interestingly, a combination of HFD and STZ for simulation of type 2 diabetes accelerated development of retinal acellular capillaries and barrier dysfunction [41,42]. Inhibition of caspase-1 or deletion of IL-1 receptor prevented IL-1β-dependent formation of acellular capillaries in retinas of type 1 diabetic mouse models [27].…”

hsa_circ_0058092 protects against hyperglycemia‑induced endothelial progenitor cell damage via miR‑217/FOXO3

“…Impaired wound healing is a major complication of diabetes mellitus (DM) and despite the associated risks, treatment strategies for diabetic-related wounds are limited. Endothelial dysfunction is an indicator of diabetes-induced macrovascular complications ( 1 , 2 ). Vascular differentiation at injury sites affects the speed of wound healing, while the homing and angiogenic differentiation of endothelial progenitor cells (EPCs) are critical for successful wound healing ( 3 ).…”