Brown adipose tissue (BAT) is an energy-expending organ that produces heat. Expansion or activation of BAT prevents obesity and diabetes. Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1 (UCP1) activation triggered via a β-adrenergic pathway. Here, we report that the cold-sensing transient receptor potential melastatin 8 (TRPM8) is functionally present in mouse BAT. Challenging brown adipocytes with menthol, a TRPM8 agonist, up-regulates UCP1 expression and requires protein kinase A activation. Upon mimicking long-term cold exposure with chronic dietary menthol application, menthol significantly increased the core temperatures and locomotor activity in wild-type mice; these effects were absent in both TRPM8(-/-) and UCP1(-/-) mice. Dietary obesity and glucose abnormalities were also prevented by menthol treatment. Our results reveal a previously unrecognized role for TRPM8, suggesting that stimulation of this channel mediates BAT thermogenesis, which could constitute a promising way to treat obesity.

High salt intake is a major risk factor for hypertension and is associated with cardiovascular events. Most countries exhibit a traditionally high salt intake; thus, identification of an optimal strategy for salt reduction at the population level may have a major impact on public health. In this multicenter, random-order, double-blind observational and interventional study, subjects with a high spice preference had a lower salt intake and blood pressure than subjects who disliked spicy food. The enjoyment of spicy flavor enhanced salt sensitivity and reduced salt preference. Salt intake and salt preference were related to the regional metabolic activity in the insula and orbitofrontal cortex (OFC) of participants. Administration of capsaicin-the major spicy component of chili pepper-enhanced the insula and OFC metabolic activity in response to high-salt stimuli, which reversed the salt intensity-dependent differences in the metabolism of the insula and OFC. In animal study, OFC activity was closely associated with salt preference, and salty-taste information processed in the OFC was affected in the presence of capsaicin. Thus, interventions related to this region may alter the salt preference in mice through fiber fluorometry and optogenetic techniques. In conclusion, enjoyment of spicy foods may significantly reduce individual salt preference, daily salt intake, and blood pressure by modifying the neural processing of salty taste in the brain. Application of spicy flavor may be a promising behavioral intervention for reducing high salt intake and blood pressure.

Background/Aims: Obesity and high salt intake are major risk factors for hypertension and cardiometabolic diseases. Obese individuals often consume more dietary salt. We aim to examine the neurophysiologic effects underlying obesity-related high salt intake. Methods: A multi-center, random-order, double-blind taste study, SATIETY-1, was conducted in the communities of four cities in China; and an interventional study was also performed in the local community of Chongqing, using brain positron emission tomography/computed tomography (PET/CT) scanning. Results: We showed that overweight/obese individuals were prone to consume a higher daily salt intake (2.0 g/day higher compared with normal weight individuals after multivariable adjustment, 95% CI, 1.2-2.8 g/day, P < 0.001), furthermore they exhibited reduced salt sensitivity and a higher salt preference. The altered salty taste and salty preference in the overweight/obese individuals was related to increased activity in brain regions that included the orbitofrontal cortex (OFC, r = 0.44, P= 0.01), insula (r = 0.38, P= 0.03), and parahippocampus (r = 0.37, P= 0.04). Conclusion: Increased salt intake among overweight/obese individuals is associated with altered salt sensitivity and preference that related to the abnormal activity of gustatory cortex. This study provides insights for reducing salt intake by modifying neural processing of salty preference in obesity.

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We use the Hill function to analyze the dynamics of Tc-99m 2 methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy data and to examine the earlier lower extremity microvascular perfusion of diabetic patients without typical clinical symptoms and with the preserved normal ankle-brachial index (ABI).Eighty-eight participants (30 healthy control, 34 diabetic patients, and 24 diabetic patients with peripheral arterial disease [PAD]) were recruited and applied 99mTc-MIBI scintigraphy. Fourteen diabetic patients with PAD also underwent computed tomography angiography (CTA) examination and were performed endovascular interventions.Diabetic patients with normal ABI already have significantly impaired maximum 99mTc-MIBI muscle perfusion counts (P < .001) and the peak times of the lower extremity muscle perfusion (P < .05). 99mTc-MIBI scintigraphy showed great consistent with ABI and CTA in detecting PAD. 99mTc-MIBI scintigraphy was also found to be effective in evaluating lower extremity circulation after endovascular interventions (P < .05).Hill function-based analysis of 99mTc-MIBI scintigraphy might be effective method to evaluate earlier lower extremity perfusion changes in diabetic patients.

Sarcoidosis has significant heterogeneity involving multiple organs; treatment of the disease is a significant therapeutic challenge due to the difficulties in accurately monitoring disease activity and estimating prognosis. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) plays an important role in assessing the metabolic activity. However, there is not enough evidence about the influence of this method in the clinical management and prognosis prediction for sarcoidosis. This study aims to investigate the clinical utility of 18F-FDG PET/CT for therapeutic evaluation and prognostic prediction in sarcoidosis. We had retrospectively enrolled 23 patients with sarcoidosis assigned to receive systemic glucocorticoids. All patients underwent baseline 18F-FDG PET/CT before initiating therapy and follow-up 18F-FDG PET/CT within 3 months after the therapy. The metabolic and clinical responses were classified. The baseline 18F-FDG PET/CT showed increased uptake in all patients. Based solely on biopsy-proven sites, the sensitivity of 18F-FDG PET/CT was 91.7%, and the sensitivity improved to 100% after excluding skin involvement. In the subsequent follow-up PET scans within 3 months after glucocorticoids therapy, the SUVmax were variously decreased except one; there are significant differences in the clinical remission rates and the relapse rates between patients with a favorable response and cases with no response on follow-up PET scan, the increasing metabolic response was associated with the increase in clinical remission rates and the reduction in recurrence rates. In conclusion, the present study shows that 18F-FDG PET/CT is an effective way to monitor the early therapeutic reaction and is helpful in predicting the long-term prognosis of sarcoidosis.

Purpose To investigate the potential of maximum standardized uptake value (SUVmax) in predicting epidermal growth factor receptor ( EGFR ) mutation status in non-small cell lung cancer (NSCLC) patients. Methods Clinical data of 311 NSCLC patients who had undergone both EGFR mutation test and 18 F-FDG PET/CT scans between January 2013 and December 2017 at our hospital were retrospectively analyzed. Patients were sub-grouped by their origin of SUVmax. Univariate and multivariate analyses were performed to investigate the association between clinical factors and EGFR mutations. Receiver operating characteristic curve (ROC) analysis was performed to confirm the predictive value of clinical factors. In vitro experiments were performed to confirm the correlation between EGFR mutations and glycolysis. Results EGFR -mutant patients had higher SUVmax than the wild-type patients in both primary tumors and metastases. In the multivariate analysis, SUVmax, gender and histopathologic type were determined as independent predictors of EGFR mutation status for patients whose SUVmax were obtained from the primary tumors; while for patients whose SUVmax were obtained from the metastases, SUVmax, smoking status and histopathologic type were regarded as independent predictors. ROC analysis showed that SUVmax of the primary tumors (cut off >10.92), not of the metastases, has better predictive value than other clinical factors in predicting EGFR mutation status. The predict performance was improved after combined SUVmax with other independent predictors. In addition, our in vitro experiments demonstrated that lung cancer cells with EGFR mutations have higher aerobic glycolysis level than wild-type cells. Conclusion SUVmax of the primary tumors has the potential to serve as a biomarker to predict EGFR mutation status in NSCLC patients.

A majority of blast-induced mild traumatic brain injury (mTBI) patients experience persistent neurological dysfunction with no findings on conventional structural MR imaging. It is urgent to develop advanced imaging modalities to detect and understand the pathophysiology of blast-induced mTBI. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) could detect neuronal function and activity of the injured brain, while MR spectroscopy provides complementary information and assesses metabolic irregularities following injury. This study aims to investigate the effectiveness of combining 18F-FDG PET with MR spectroscopy to evaluate acute and subacute metabolic cerebral alterations caused by blast-induced mTBI. Thirty-two adult male Sprague–Dawley rats were exposed to a single blast (mTBI group) and 32 rats were not exposed to the blast (sham group), followed by 18F-FDG PET, MRI, and histological evaluation at baseline, 1–3 h, 1 day, and 7 days post-injury in three separate cohorts. 18F-FDG uptake showed a transient increase in the amygdala and somatosensory cortex, followed by a gradual return to baseline from day 1 to 7 days post-injury and a continuous rise in the motor cortex. In contrast, decreased 18F-FDG uptake was seen in the midbrain structures (inferior and superior colliculus). Analysis of MR spectroscopy showed that inflammation marker myo-inositol (Ins), oxidative stress marker glutamine + glutamate (Glx), and hypoxia marker lactate (Lac) levels markedly elevated over time in the somatosensory cortex, while the major osmolyte taurine (Tau) level immediately increased at 1–3 h and 1 day, and then returned to sham level on 7 days post-injury, which could be due to the disruption of the blood–brain barrier. Increased 18F-FDG uptake and elevated Ins and Glx levels over time were confirmed by histology analysis which showed increased microglial activation and gliosis in the frontal cortex. These results suggest that 18F-FDG PET and MR spectroscopy can be used together to reflect more comprehensive neuropathological alterations in vivo, which could improve our understanding of the complex alterations in the brain after blast-induced mTBI.