High-fat diet-induced obesity and insulin resistance significantly increased the ex vivo uptake of [18F]FDG and [18F]FTHA in mouse kidneys compared to standard chow.
An ex vivo PET/CT protocol demonstrated that obesity and insulin resistance induced by a high-fat diet increase the uptake of [18F]FDG and [18F]FTHA in mouse kidneys, suggesting potential clinical utility for detecting incipient diabetic nephropathy.
p-value: p=<0.05
It is known that high-fat diet (HFD) and/or diabetes may influence substrate preferences and energy demands in the heart preceding diabetic cardiomyopathy. They may also induce structural glomerular changes causing diabetic nephropathy. PET/CT has been utilized to examine uptake of energy substrates, and to study metabolic changes or shifts before onset of metabolic disorders. However, conventional PET/CT scanning of organs with relatively low uptake, such as the kidney, in small animals in vivo may render technical difficulties. To address this issue, we developed a PET/CT ex vivo protocol with radiolabeled glucose and fatty acid analouges, 18FFDG and 18FFTHA,to study substrate uptake in mouse kidneys. We also aimed to detect a possible energy substrate shift before onset of diabetic nephropathy. The ex vivo protocol reduced interfering background as well as interindividual variances. We found increased uptake of 18FFDG and 18FFTHA in kidneys after HFD, compared to kidneys from young mice on standard chow. Levels of kidney triglycerides also increased on HFD. Lipoprotein lipase (LPL) activity, the enzyme responsible for release of fatty acids from circulating lipoproteins, is normally increased in postprandial mice kidneys. After long-term HFD, we found that LPL activity was suppressed, and could therefore not explain the increased levels of stored triglycerides. Suppressed LPL activity was associated with increased expression of angiopoietin-like protein4, an inhibitor of LPL. HFD did not alter the transcriptional control of some common glucose and fatty acid transporters that may mediate uptake of 18FFDG and 18FFTHA. Performing PET/CT ex vivo reduced interfering background and interindividual variances. Obesity and insulin resistance induced by HFD increased the uptake of 18FFDG and 18FFTHA and triglyceride accumulation in mouse kidneys. Increased levels of 18FFDG and 18FFTHA in obese insulin resistant mice could be used clinically as an indicator of poor metabolic control, and a complementary test for incipient diabetic nephropathy.
Nyrén et al. (Tue,) conducted a other in Obesity and insulin resistance (n=57). High-fat diet (HFD) vs. Standard chow diet was evaluated on Standardized uptake values (SUV) of [18F]FDG and [18F]FTHA in kidneys ex vivo (p=<0.05). High-fat diet-induced obesity and insulin resistance significantly increased the ex vivo uptake of [18F]FDG and [18F]FTHA in mouse kidneys compared to standard chow.