Abstract
We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on body weight and insulin resistance were measured. The retina was assessed by electroretinogram (ERG), fundus photography, permeability studies, and trypsin digests for enumeration of acellular capillaries. The HFD cohort experienced hypercholesterolemia when compared to the LFD cohort, but not hyperglycemia. HFD mice developed a higher body weight (60.33 g vs. 30.17g, p < 0.0001) as well as a reduced insulin sensitivity index (9.418 vs. 62.01, p = 0.0002) compared to LFD controls. At 6 months, retinal functional testing demonstrated a reduction in a-wave and b-wave amplitudes. At 12 months, mice on HFD showed evidence of increased retinal nerve infarcts and vascular leakage, reduced vascular density, but no increase in number of acellular capillaries compared to LFD mice. In conclusion, the HFD mouse is a useful model for examining the effect of prediabetes and hypercholesterolemia on the retina. The HFD-induced changes appear to occur slower than those observed in type 2 diabetes (T2D) models but are consistent with other retinopathy models, showing neural damage prior to vascular changes.
Highlights
Diabetes is considered a worldwide epidemic [1,2]
At 12 months, there was no difference in fasting blood glucose levels (Figure 1D, basal) and intraperitoneal glucose tolerance test (IP-GTT) did not show any significant differences between low-fat diet (LFD)
We show that high-fat diet (HFD) mice have hypercholesterolemia and insulin resistance but the absence of hyperglycemia, which is typical of type 2 diabetes (T2D) models
Summary
Diabetes is considered a worldwide epidemic [1,2]. Recent reports indicate that over 90% of diabetic individuals have type 2 diabetes (T2D) [3,4]. The most common microvascular complication of diabetes is diabetic retinopathy (DR) [2]. Cells 2020, 9, 464 completely recapitulate the metabolic phenotype [6]. The high-fat diet (HFD) mouse model has been described as a robust model for investigating obesity-associated T2D and its related metabolic complications [7]. Studies have shown that HFD-fed mice develop obesity, impaired glucose tolerance, and reduced insulin sensitivity [8,9] with systemic manifestations involving adipose tissue [10], liver [8], and kidneys [11]. The ocular changes associated with the HFD model have not been fully investigated. The typical Western diet (WD; 40% fat) has been given to rodents to recapitulate obesity-driven pathology. To mimic the features of T2D, the administration of low-dose Streptozotocin (STZ) is given to the WD mice [12,13,14]
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