Cutting the Fat.

High-fat diets (HFDs) are commonly used to induce symptoms of human metabolic syndrome, including increased adiposity, hypertension, dyslipidemia, and impaired glucose tolerance in rodent models. Although HFDs are widely available commercially for experimental purposes from several different companies, including Bio-Serv, ResearchDiets, Dyets, and Envigo to name a few, there has been considerable discrepancy in the literature regarding the definition of an HFD about both total fat content and the source of dietary fat. There is a broad spectrum in the type of fat used in HFD studies, including lard, corn oil, coconut fat, olive oil, and fish oil, that range in energy density from 20% to 60%. The lack of standardization in the amount and type of HFDs used in the literature has led to a wide degree of variability in the metabolic and cardiovascular responses reported in rodent models. This is further complicated by differences not only across strains, but within strains, as the result of dissimilarities in colony management by different vendors. Last, the effect of sex on HFD-induced metabolic and cardiovascular disease (CVD) in experimental models has not been examined nearly as much as needed. Although sex differences in salt-sensitive hypertension have been well established, women are more likely than men to had obesity, which is an independent risk factor for CVD. With this in mind, it was with great interest that we read the recently published manuscript in this issue of Hypertension by Fernandes et al, which is among the first to examine the impact of sex on HFD-induced renal alterations in Dahl saltsensitive rats (DSS) and Sprague Dawley rats. The purpose of this editorial commentary is to highlight possible sources of dissimilarities in the metabolic and cardiovascular phenotypes of DSS rats in response to an HFD. The DSS is a model commonly used to study salt-sensitive hypertension; however, recent evidence suggests that this strain also exhibits increases in blood pressure (BP) in response to a normal salt, HFD (Table). In this issue of Hypertension, the article “Sex differences in renal inflammation and injury in high-fat diet–fed hypertensive Dahl salt-sensitive rats” by Fernandes et al, the authors obtained 3-week-old male and female DSS commercially from Charles River Laboratories that when weaned onto a normal salt (0.3% NaCl) very HFD (60% kcal from fat, ResearchDiets D12492) exhibited significant increases in mean arterial pressure as measured by radiotelemetry after 17 weeks of HFD feeding relative to DSS maintained on the corresponding control low-fat diet (10% kcal from fat with matching sucrose to D12492; ResearchDiets D12450J). After 24 weeks of HF feeding, mean arterial pressure was ≈40 mm Hg higher compared with that of DSS on low-fat diet in both males and females. Although both male and female DSS on HFD exhibited increased adiposity compared with rats on normal-fat diet, HFD-induced hypertension occurred in the absence of greater increases in body weight or changes in other metabolic parameters, including blood glucose, insulin, or leptin relative to rats on normal-fat diet. Conversely, HFD did not increase mean arterial pressure in either male or female Sprague Dawley rats compared with low-fat diet. The lack of a BP response to HFD in Sprague Dawley rats is consistent with another recent report after 17 weeks of HF feeding in male Sprague Dawley rats, although the fat content of the diet was lower (45% kcal from fat), raising the potential that DSS is a unique model to study HFDinduced alterations in cardiovascular health and function. Consistent with this notion, a direct corollary to the findings by Fernandes et al, in this issue of Hypertension can be drawn to those reported previously by Spradley et al using 12-week-old male DSS from Charles River Laboratories, which also exhibited HFD-induced hypertension compared with rats on a normal diet (normal diet: Teklad 8604 with 14% kcal from fat; HFD: Bio-Serv F2685 with 59% kcal from fat). Further, there were no changes in plasma triglycerides or cholesterol, fasting blood glucose, or insulin; but serum leptin levels were elevated in accordance with an increase in body weight and visceral fat pads (epididymal and perirenal) in response to HFD. In contrast, Fernandes et al did not report an increase in body weight with HFD compared with control low-fat diet in the DSS. The most notable difference in experimental outcomes between these 2 studies, however, was that a mean arterial pressure elevation of ≈30 mm Hg as measured via telemetry was achieved after 4 weeks of HFD in the study by Spradley et al, as compared with the ≈24 weeks of HFD that was required to induce a comparable effect in the study by Fernandes et al. Of interest, although the caloric density of the 2 HFDs was comparable (60% kcal from fat), the dietary fat source in ResearchDiet D12492 The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Department of Physiology, Augusta University, GA. Correspondence to Jennifer C. Sullivan, Department of Physiology, Augusta University, 1459 Laney Walker Blvd, Augusta, GA 30912. Email jensullivan@augusta.edu Cutting the Fat Dissecting Sources of Variability in Cardiovascular and Metabolic Phenotypes of High-Fat Fed Dahl Salt-Sensitive Rats