High-fat diet alters fluid intake without reducing sensitivity to glucagon-like peptide-1 receptor agonist effects

Rats that are maintained on a high-fat diet (HFD) differ from controls in many ways, but how HFD maintenance affects water intake and drinking behavior has not been well studied. This is unfortunate because diet and obesity may influence fluid balance in humans through a mechanism that is poorly understood. We therefore tested the hypothesis that HFD maintenance affects water intake in rats. Water intake and drinking behavior are, in part, controlled by the actions of glucagon-like peptide-1 (GLP-1), a peptide which is well studied for its hypophagic effects. Previous studies have shown that HFD maintenance impairs the ability of GLP-1 receptor agonists to suppress food intake when the drug is administered peripherally, but not centrally. The effects of GLP-1 on fluid intake are thought to rely more on central receptor activation; therefore, a secondary aim of these experiments was to shed additional light on the location of GLP-1 responsive cells that mediate feeding vs drinking behavior. We maintained male Sprague-Dawley rats on HFD or low-fat diet (LFD) for six weeks and measured body weight, food intake, water intake, and drinking behavior. We then tested the relative contributions of diet and body weight on food intake and water intake after peripheral and central injections of GLP-1 receptor agonist Exendin-4 (Ex4). We found that HFD maintenance reduced the amount of water consumed, when intake was corrected for body weight. Consistent with other reports, rats on HFD showed a smaller suppression of food intake when given Ex4 peripherally, but not centrally. Water intake suppression when given Ex4 did not differ by diet or body weight regardless of injection site, however, adding support to the hypothesis that only central GLP-1 receptors are involved in water intake.