Archive for the ‘Journal of Clinical Investigation’ Category

Circulating glucose levels modulate neural control of desire for high-calorie foods in humans

September 21, 2011 Comments off

Circulating glucose levels modulate neural control of desire for high-calorie foods in humans
Source: Journal of Clinical Investigation

Obesity is a worldwide epidemic resulting in part from the ubiquity of high-calorie foods and food images. Whether obese and nonobese individuals regulate their desire to consume high-calorie foods differently is not clear. We set out to investigate the hypothesis that circulating levels of glucose, the primary fuel source for the brain, influence brain regions that regulate the motivation to consume high-calorie foods. Using functional MRI (fMRI) combined with a stepped hyperinsulinemic euglycemic-hypoglycemic clamp and behavioral measures of interest in food, we have shown here that mild hypoglycemia preferentially activates limbic-striatal brain regions in response to food cues to produce a greater desire for high-calorie foods. In contrast, euglycemia preferentially activated the medial prefrontal cortex and resulted in less interest in food stimuli. Indeed, higher circulating glucose levels predicted greater medial prefrontal cortex activation, and this response was absent in obese subjects. These findings demonstrate that circulating glucose modulates neural stimulatory and inhibitory control over food motivation and suggest that this glucose-linked restraining influence is lost in obesity. Strategies that temper postprandial reductions in glucose levels might reduce the risk of overeating, particularly in environments inundated with visual cues of high-calorie foods.

See: To Ditch Dessert, Feed the Brain (Science Daily)

Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice

July 21, 2011 Comments off

Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice
Source: Journal of Clinical Investigation

In addition to its role as an essential neurotransmitter, dopamine serves important physiologic functions in organs such as the kidney. Although the kidney synthesizes dopamine through the actions of aromatic amino acid decarboxylase (AADC) in the proximal tubule, previous studies have not discriminated between the roles of extrarenal and intrarenal dopamine in the overall regulation of renal function. To address this issue, we generated mice with selective deletion of AADC in the kidney proximal tubules (referred to herein as ptAadc–/– mice), which led to selective decreases in kidney and urinary dopamine. The ptAadc–/– mice exhibited increased expression of nephron sodium transporters, decreased natriuresis and diuresis in response to l-dihydroxyphenylalanine, and decreased medullary COX-2 expression and urinary prostaglandin E2 excretion and developed salt-sensitive hypertension. They had increased renin expression and altered renal Ang II receptor (AT) expression, with increased AT1b and decreased AT2 and Mas expression, associated with increased renal injury in response to Ang II. They also exhibited a substantially shorter life span compared with that of wild-type mice. These results demonstrate the importance of the intrarenal dopaminergic system in salt and water homeostasis and blood pressure control. Decreasing intrarenal dopamine subjects the kidney to unbuffered responses to Ang II and results in the development of hypertension and a dramatic decrease in longevity.


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