The relationship between hypothalamic and hepatic response to a high-fat diet in relation to insulin sensitivity and leptin action

B De Roos, Eva-Maria Bachmair, M Boekschoten, C D Mayer, M Muller, L Williams

Research output: Contribution to journalAbstract

Abstract

Aims: Multi-organ transcriptome and proteome measurements in combination with advanced bioinformatics may allow us to uncover how a complex organism copes with the dietary stress of excess saturated fat, gaining insight into both metabolic health and dietary induced disease development.

Methods: In this study we assessed the response to a 1 and 4 week high- (45% of energy from saturated fat) or low- (10% of energy by saturated fat) fat dietary intervention, with or without a 24-hr leptin challenge before the cull, on changes in the hypothalamus transcriptome, the hepatic proteome, hepatic lipid accumulation and serum markers of insulin and leptin sensitivity in C57Bl/6 mice.

Results: Body weight gain and blood glucose levels were significantly increased by the high-fat diet, compared to the low-fat diet, with time (p< 0.05), but were not affected by the leptin challenge. This challenge did, however, decrease liver weight after 1 week, but only in mice on the low-fat diet (p< 0.05). The leptin challenge only induced changes in the hypothalamic transcriptome after intervention with the low-fat diet, with 26 genes being significantly regulated. Hepatic proteome analysis and fat accumulation, as well as plasma analyses of leptin, insulin, resistin, adiponectin, PAI-1, IL-6, TNF-alpha and MCP-1 are currently being performed.

Conclusions: This design enables us to concurrently map changes in the hypothalamus and liver in mice stressed by a high-fat diet, and elucidate interactions between leptin and diet with regard to hepatic steatosis and leptin insensitivity in the hypothalamus.
Original languageEnglish
Pages (from-to)A70
Number of pages1
JournalJournal of Diabetes
Volume1
Issue numberS1
Early online date25 Feb 2009
DOIs
Publication statusPublished - Apr 2009

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