The Impact of Maternal High-Fat Feeding on Liver and Abdominal Fat Accumulation in Adult Offspring Under a Long-Term High-Fat Diet

ADRIANA L. BURGUEÑO; JULIETA CARABELLI; SILVIA SOOKOIAN; CARLOS J. PIROLA

HEPATOLOGY (BALTIMORE, MD.)

JOHN WILEY & SONS INC

Año: 2010 vol. 51 p. 2234 - 2235

0270-9139

We read with great interest the article by Bruce et al. regarding theeffect in a mouse model of maternal high-fat feeding on the developmentof nonalcoholic fatty liver disease (NAFLD) in adult offspring.1The authors observed that maternal fat intake contributes toward theNAFLD progression in adult offspring, which is mediated throughimpaired hepatic mitochondrial metabolism. Although the authorsreported only female mice data because their data from males andfemales showed the same pattern, we consider that some issues deservefurther discussion.We evaluated in a rat model the impact of developmental andlong-term adult nutritional insult of high-fat diet (HFD) on liversteatosis and abdominal fat accumulation, and compared male andfemale offspring of dams exposed to different nutrition treatments(HFD versus standard chow diet [SCD]) to examine the hypothesisthat nutritional insults during fetal development can result in a fattyliver phenotype in adulthood. Interestingly, we replicated the findingsof Bruce et al., and observed in addition that maternal HFD feedingmodified the sexual dimorphic effect of HFD on liver steatosis andabdominal fat content observed in offspring of mothers fed an SCD.Female Wistar rats were randomly assigned to either ad libitumHFD solid diet2 or SCD. Dams were fed 15 days before conceptionand during gestation and lactation. The 17-week-old offspring wereassigned either ad libitum HFD or SCD for an 18-week period, generatingeight experimental groups (Fig. 1). At the completion of thestudy, animals were sacrificed and abdominal fat tissue (intraperitonealand retroperitoneal) was measured by direct weighing; the degree ofliver steatosis was assessed as previously reported.3In the group of HFD-fed offspring of SCD-fed dams, we observeda clear sexually dimorphic effect of HFD feeding because female ratsdeveloped a significantly greater degree of fatty change than male rats;this finding was similar when we analyzed abdominal fat content (Fig.1). However, in the group of HFD-fed offspring of HFD-fed dams,the sexual differences in both fatty liver degree and abdominal fatcontent were not observed, although the degree of liver steatosis waslower in female offspring of HFD-fed dams versus those of SCD-feddams (Fig. 1). Interestingly, these effects were independent of dambody weight, which suggests a specific effect of the diet.In conclusion, the female-specific consequences of feeding HFD (afinding previously reported in other rat models of NAFLD4) deservesfurther investigations as the underlying mechanism involved in the sexdifference are not clear. Otherwise, our study provides additional evidenceof the effect of maternal high-fat nutrition on the liver andabdominal fat accumulation in either male or female HFD-fed offspring,thus suggesting the importance of the developmental programmingthat can induce the NAFLD phenotype completely independentof sex differences. This finding strongly supports the hypothesis ofBruce et al. about the “priming” effect of maternal mitochondria onmetabolic pathways associated with NAFLD, which is compatiblewith our recent findings of a decrease in mitochondrial DNA copynumber in adolescents with insulin resistance5 and in newborns withabnormal birth weight,6 which are two well-known risk factors formetabolic syndrome in adults