Differential Effects of Dietary Lipid Content and Composition on Gene Expression in the Hypothalamus and Pituitary

Presentation Number: MON-0386
Date of Presentation: June 23rd, 2014

Brian M Shewchuk*1 and Patti R Shaver2
1East Carolina University School of Medicine, Greenville, NC, 2East Carolina University School of Medicine


Obesity is a risk factor for developing the characteristics of metabolic syndrome (MetS), which include insulin resistance, hyperglycemia, hypertension, dyslipidemia and inflammation, and is associated in part with a diet rich in saturated fats.  In contrast, evidence suggests that a diet rich in n-3 polyunsaturated fatty acids (n-3 PUFA) may prevent some of the comorbidities of MetS. Some features of MetS are due to altered function in peripheral tissues, but CNS effects such as insensitivity to peripheral metabolic signals or changes in hypothalamic and pituitary peptides are also thought to contribute. We hypothesize that these central effects may include broadly altered gene expression in the hypothalamus and pituitary, which has the potential to impinge on a range of physiological functions that may contribute to the pathophysiology of MetS. In the present study, we addressed the potential for high fat diet and n-3 PUFAs to affect the expression of selected hypothalamic and pituitary hormone and hormone receptor genes in a mouse model of diet-induced obesity. Six-week-old male C57BL/6 mice were fed either a low fat control diet, or diets high in saturated fat alone or supplemented with fish oil as a crude source of long chain PUFAs, or purified ethyl esters of the n-3 PUFAs docosahexaenoic acid (22:6n-3, DHA) or eicosapentaenoic acid (20:5n-3, EPA). By 5 weeks of feeding, mice fed a high fat diet had significantly increased body mass compared to low fat diet controls that was independent of the specific lipid composition.  This effect was magnified by 10 weeks, when pituitary and hypothalamic RNA was purified for analysis by qRT-PCR. The high fat diet resulted in significantly altered levels of multiple pituitary and hypothalamic transcripts compared to the low fat diet controls, with both positive and negative effects observed. The effects were dependent on the lipid composition, with fish oil, DHA, and EPA significantly modifying the effects of the high fat diet. These preliminary findings suggest that a lipid-responsive mechanism can directly or indirectly affect gene transcription in the hypothalamus and pituitary, and appears to be sensitive to the specific lipid composition of the diet. These effects have the potential to alter the function of the hypothalamic-pituitary axis in the context of diet-induced obesity, and may represent a significant component of the progression of metabolic syndrome and the protective effects of n-3 PUFAs.


Nothing to Disclose: BMS, PRS