Fructose Consumption During Pregnancy Influences Milk Lipid Composition and Offspring Lipid Profiles in Guinea Pigs

Abstract

Excess dietary fructose is a major public health concern ( 1 – 4 ). Evidence shows increased fructose intake can cause insulin resistance, hepatic de novo lipogenesis, hypertriglyceridemia, obesity and non-alcoholic fatty liver disease (NAFLD) ( 5 – 9 ). However, little is known about the effects of fructose during pregnancy and its influence on offspring development and predisposition to later-life disease. To determine whether moderately increased maternal fructose intake could have health consequences on offspring, we have investigated the effects of 10% w/v fructose water intake during preconception and pregnancy. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD;10% kcal from fructose) ad-libitum 60 days prior to mating and throughout gestation. Offspring were culled at weaning, day 21 (d21). Compared to CD dams, FD dams had altered glucose metabolism and increased milk free fatty acid content. Matsuda-DeFronzo insulin sensitivity index (M-ISI) from OGTT plasma showed no significant difference in whole-body insulin sensitivity between FD and CD dams 60 days post-dietary intervention and during midgestation. Fetal exposure to increased maternal fructose resulted in offspring with significantly altered serum free fatty acids at days 0, 7, 14, and 21 [including pentadecanoic acid (15:0), dma16:0, margaric acid (17:0) palmitoleic acid, total omega-7 and total saturates], increased levels of uric acid and triglycerides were also observed at d21. We have demonstrated that increased fructose intake during pregnancy can cause significant changes in maternal metabolic function and milk composition, which alters offspring metabolism. Taken together, these changes in pregnancy outcomes and feto-maternal condition may underlie their offspring's predisposition to metabolic dysfunction during later-life.

Pregnancy Is Enough to Provoke Deleterious Effects in Descendants of Fructose-Fed Mothers and Their Fetuses

“…Curiously, in the present study, although total calories ingested by FF dams during gestation were higher than the calorie intake by CC or FC groups, body weight at day 21 of pregnancy and body weight increase during gestation did not show changes between the three experimental groups. Similar results related to the higher liquid intake and the enhanced total amount of ingested energy due to fructose consumption during gestation with no changes in maternal body weight have been previously recorded in rodents [ 24 , 41 ]. Interestingly, no changes in the amount of chow or liquid diet ingested nor body weight during gestation were seen in FC pregnant rats when compared to controls (CC), which means that maternal fructose intake does not seem to affect the progression of gestation in the progeny.…”

“…Surprisingly, levels of adiponectin, another adipokine, were increased in pregnant rats from fructose-fed mothers regardless of the treatment that they had received during pregnancy. Although reductions in adiponectinemia have been related to insulin resistance in rats receiving fructose or high-fat diets [ 40 , 41 ], we have previously reported increments in adiponectin levels both in fructose-fed pregnant rats [ 26 ] and in non-pregnant descendants from fructose-fed mothers with and without re-exposure to fructose [ 29 , 30 ]. Since it is known that adiponectin is able to improve insulin sensitivity [ 39 ], we attributed these increments in adiponectinemia to an attempt to preserve the insulin sensitivity in the livers of these animals.…”

Maternal Fructose Diet-Induced Developmental Programming

“…Markers of hepatic inflammation also increase in offspring following maternal HF diet exposure [ 31 ]. Similarly, HF feeding in guinea pigs prior to—and during—pregnancy resulted in offspring with significantly altered serum free fatty acids, and increased levels of uric acid and triglycerides, all of which developed before weaning [ 32 ].…”

Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring

“…The dams' water was additionally supplemented with 10% fructose water (Fructose group) from 12 weeks to birth (~69 days of pregnancy). Dam caloric intake and weight gain were recorded and published [7].…”

“…Fructose has become a major public health concern due to the associated increase of metabolic diseases such as; dyslipidemia, hyperlipidemia, insulin resistance, visceral adiposity, obesity, diabetes, high blood pressure, cardiovascular disease and non-alcoholic fatty liver disease (NAFLD) [1][2][3][4][5][6][7]. When considering the impact of fructose on the prevalence of metabolic disease, several factors appear clear.…”