Clin Nutr Res.  2018 Oct;7(4):276-290. 10.7762/cnr.2018.7.4.276.

Effects of Maternal and Post-Weaning High-Fat Diet on Leptin Resistance and Hypothalamic Appetite Genes in Sprague Dawley Rat Offspring

• Choi JS

• KMID: 2424303
• DOI: http://doi.org/10.7762/cnr.2018.7.4.276

Abstract

The defective satiation signaling may contribute to the etiology of obesity. We investigated how dietary modification during maternal (pregnancy and lactation) and post-weaning affects obesity, insulin resistance (IR) and hypothalamic appetite responses in offspring in adulthood. Pregnant female SD rats were randomly allocated to either maternal high-fat diet (43% energy from fat) or control diet (12% energy from fat) until the end of suckling. After weaning for additional 4 weeks, half of the offsprings were continuously fed the same diet as the dam (C-C and H-H groups); the remainder received the counterpart diet (C-H and H-C groups). The long-term high-fat diet during maternal and post-weaning period (H-H group) led to susceptibility to obesity and IR through the significant increases of hypothalamic orexigenic genes compared to the maternal and post-weaning control diet group (C-C group). In contrast, the hypothalamic expression levels of anorexigenic genes, apolipoprotein E, leptin receptor, and activated signal transducer and activator of transcription protein 3 were significantly lower in H-H group with elevations in circulating insulin and leptin and body fat mass. However, dietary changes after weaning (H-C and C-H groups) partially modified these conditions. These results suggest that maternal and post-weaning diet conditions can potentially disrupt hypothalamic neuronal signal irrelevantly, which is essential for leptin's regulation of energy homeostasis and induce the risk of offspring to future metabolic disorders.

Keyword

High-fat diet; Pregnancy; Weaning; Appetite; Leptin

MeSH Terms

Adipose Tissue
Animals
Apolipoproteins
Appetite*
Diet
Diet, High-Fat*
Female
Food Habits
Homeostasis
Humans
Insulin
Insulin Resistance
Leptin*
Neurons
Obesity
Pregnancy
Rats*
Receptors, Leptin
Satiation
Transducers
Weaning
Apolipoproteins
Insulin
Leptin
Receptors, Leptin

Figure

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  Fig. 1 Energy intake (A), body mass (B), and fat mass (C). Values are mean ± standard error (n = 6 per sex per group). *,†,‡Groups with different marks are significantly different at p < 0.05.

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  Fig. 2 Glucose tolerance (A, B), plasma glucose (C), insulin (D), IR index (E) and leptin (F) levels. Values are mean ± standard error (n = 6 per sex per group). IR, insulin resistance. *,†,‡Groups with different marks are significantly different at p < 0.05.

• 

  Fig. 3 NPY (A, B), AgRP (C, D), POMC (E, F), CART (G, H), and ApoE (I, J) mRNA levels in the hypothalamus. Values are mean ± standard error (n = 6 per sex per group). NPY, neuropeptide Y; AgRP, agouti-related protein; POMC, pro-opiomelanocortin; CART, cocaine and amphetamine related transcript; ApoE, apolipoprotein E. *,†,‡,§Groups with different marks are significantly different at p < 0.05.

• 

  Fig. 4 LepR (A, B) and STAT3 phosphorylation (C, D) in the hypothalamus. (A, C) are the results for males and (B, D) are the results for females. Values are mean ± standard error (n = 6 per sex per group). LepR, leptin receptor; STAT3, signal tranducer and activator of transcription protein 3; pSTAT3, phosphorylation of STAT3. *,†,‡Groups with different marks are significantly different at p < 0.05.

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