Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats

Abstract

Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose (FR) and low-protein (LP) diets are linked to hepatic steatosis and insulin resistance in nonpregnant animals. We hypothesized that dietary FR or LP intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of LP or FR intake on hepatic steatosis and insulin resistance in unmated controls (CTs) and pregnant and lactating rats. Sprague-Dawley rats were fed a CT, or a 63% FR, or an 8% LP diet. Glucose tolerance test at day 17 of the study revealed greater (P < .05) blood glucose at 10 (75.6 mg/dL vs 64.0 ± 4.8 mg/dL) minutes and 20 (72.4 mg/dL vs 58.6 ± 4.0 mg/dL) minutes after glucose dose and greater area under the curve (4302.3 mg∙dL(-1)∙min(-1) vs 3763.4 ± 263.6 mg∙dL(-1)∙min(-1)) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < .05) livers (9.3%, 7.1% body weight vs 4.8% ± 0.2% body weight) and elevated (P < .05) liver triacylglycerol (216.0, 130.0 mg/g vs 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. Fructose induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated CT rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than an LP diet.

Figure 1

Representative H&E staining of rat liver after 6 weeks of dietary treatment. Unmated female Sprague-Dawley rats (a, c, e) and 3-day-pregnant Sprague-Dawley rats (b, d, f) were fed either a control (a, b), a fructose (c, d) or a low protein (e, f) diet for 6 weeks. Liver samples were collected at the end of the diet treatment and stained with H&E. Representative Liver sample from rat dams fed the fructose diet was infiltrated with lipid droplets (d) compared with the liver sample from dams fed the control diet (b). Low protein feeding to the dams (f) also resulted in lipid droplet accumulation in the liver compared with the control diet, but the consequence was not as pronounced as fructose feeding. The central vein (CV) and portal vein (PV) and indicated where visible and the lipid droplets indicated within panels d and f, magnification for all panels is 100×.