The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation.

We are facing an obesity epidemic, and obesity itself and its close companion, type 2 diabetes, are independent risk factors for neurodegeneration. While most medical treatments fail to induce a clinically meaningful improvement in neurodegenerative disorders, lifestyle interventions have emerged in the spotlight. A recently rediscovered approach is intermittent fasting (IF), which, compared to the classic caloric restriction regimens, limits only the time of eating, rather than the number of calories allowed per day. There is already a large amount of evidence from preclinical and clinical studies showing the beneficial effects of IF. In this review, we specifically focus on the effects of IF on brain metabolism. Key molecular players modified during IF and involved in its beneficial central effects (ketone bodies, BDNF, GABA, GH/IGF-1, FGF2, sirtuin-3, mTOR, and gut microbiota) are identified and discussed. Studies suggest that IF induces several molecular and cellular adaptations in neurons, which, overall, enhance cellular stress resistance, synaptic plasticity, and neurogenesis. Still, the absence of guidelines regarding the application of IF to patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge on the different IF protocols and long-term effects of IF on brain metabolism before it can be widely prescribed.

OBJECTIVE Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of study participants across a wide range of age and insulin sensitivity. RESEARCH DESIGN AND METHODS [¹⁸F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 participants scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acid levels, C-reactive protein levels, HbA_1c, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. RESULTS Insulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin-resistant participants BGU was enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with additional increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein and free fatty acid levels, sex, and HbA_1c were not associated with BGU. CONCLUSIONS In this large cohort of participants of either sex across a wide range of age and insulin sensitivity, insulin sensitivity was the best predictor of BGU.

Imaging brain glucose metabolism with fluorine-labelled fluorodeoxyglucose ([¹⁸F]-FDG) positron emission tomography (PET) has long been utilized to aid the diagnosis of memory disorders, in particular in differentiating Alzheimer’s disease (AD) from other neurological conditions causing cognitive decline. The interest for studying brain glucose metabolism in the context of metabolic disorders has arisen more recently. Obesity and type 2 diabetes—two diseases characterized by systemic insulin resistance—are associated with an increased risk for AD. Along with the well-defined patterns of fasting [¹⁸F]-FDG-PET changes that occur in AD, recent evidence has shown alterations in fasting and insulin-stimulated brain glucose metabolism also in obesity and systemic insulin resistance. Thus, it is important to clarify whether changes in brain glucose metabolism are just an epiphenomenon of the pathophysiology of the metabolic and neurologic disorders, or a crucial determinant of their pathophysiologic cascade. In this review, we discuss the current knowledge regarding alterations in brain glucose metabolism, studied with [¹⁸F]-FDG-PET from metabolic disorders to AD, with a special focus on how manipulation of insulin levels affects brain glucose metabolism in health and in systemic insulin resistance. A better understanding of alterations in brain glucose metabolism in health, obesity, and neurodegeneration, and the relationships between insulin resistance and central nervous system glucose metabolism may be an important step for the battle against metabolic and cognitive disorders.

Aim: To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Materials and Methods: Patients with type 2 diabetes on metformin treatment were randomized to double‐blind, 6‐week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [ ¹¹ C]‐acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [ ¹⁸ F]‐6‐thia‐heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. Results: Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m ² and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (−0.095 [−0.145, −0.043] J/g/min) and LV oxygen consumption were significantly reduced (−0.30 [−0.49, −0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was −3.19 (−6.32, −0.07) mL/m ² ( p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (−3.92% [−7.57%, −0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] μmol/g/min; p = .018), while cardiac uptake was unchanged. Conclusions: This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.