Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

Abstract

Background: There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet.

Methods: Female Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured.

Results: Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups.

Conclusions: Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

Figure 1

Research protocol of the experiment. The rats were divided into three groups. The arrows indicate the times of blood draws and isotope infusion. A vaginal smear was administrated everyday since 8 weeks.

Figure 2

Experimental setting for stable isotope infusion. The rats catheterized in the tail artery for blood collection and in the tail vein for isotope infusion. The rats were relaxed, with the ability to move partially, groom and drink. Thus, experimental stress was minimized.

Figure 3

Protocol of in vivo infusions of stable isotopes. This is the protocol of steady-state isotope infusion. The arrows indicate the times for blood draws and tissue sampling.

Figure 4

Body weight and blood glucose levels in three groups. Since 3 weeks of age, body weight measurements and blood glucose levels were taken every week. A: body weight changes in the 3 groups; B: blood glucose levels in the 3 groups.

Figure 5

The main stages of the reproductive cycle in the control rats. Swab smears (unstained) shown with the original microscope magnification of 100×. A:Estrus stage: large cornified cells in clumps. B: Metestrus stage: large numbers of leucocytes with smaller numbers of non-nucleated epithelial cells (note characteristic clumping together of two cell types at the center-right). C: Diestrus stage: predominantly leucocytes with a small number of epithelial and cornified cells. D: Proestrus stage:epithelial cells are mostly rounded but some cells shows early stages of cornification of approaching estrus.

Figure 6

Histology of ovaries. Ovaries were stained by HE staining:A:control group(HE staining, ×40); B:andronate group(×40); C:andronate + HFD group(×40); D:control group(×200); E:andronate group(×200); F:andronate + HFD group(×200).

Figure 7

Body hair in the three rats groups. At 10 weeks of age, pictures were taken of the 3 groups. A:control group; B:andronate group; C:andronate with HFD group.

Figure 8

FBG, FINS, HOMA-IR and ISI in the 3 groups. Tail blood was obtained after an overnight fast in 10-week-old rats to assess fasting blood glucose (FBG), fasting plasma insulin (FINS), homeostasis model-insulin resistance (HOMA-IR) and insulin sensitivity index(ISI) in 3 groups.