Analysing the Cyanobacterial PipX Interaction Network Using NanoBiT Complementation in Synechococcus elongatus PCC7942.

The conserved cyanobacterial protein PipX is part of a complex interaction network with regulators involved in essential processes that include metabolic homeostasis and ribosome assembly. Because PipX interactions depend on the relative levels of their different partners and of the effector molecules binding to them, in vivo studies are required to understand the physiological significance and contribution of environmental factors to the regulation of PipX complexes. Here, we have used the NanoBiT complementation system to analyse the regulation of complex formation in Synechococcus elongatus PCC 7942 between PipX and each of its two best-characterized partners, PII and NtcA. Our results confirm previous in vitro analyses on the regulation of PipX-PII and PipX-NtcA complexes by 2-oxoglutarate and on the regulation of PipX-PII by the ATP/ADP ratio, showing the disruption of PipX-NtcA complexes due to increased levels of ADP-bound PII in Synechococcus elongatus. The demonstration of a positive role of PII on PipX-NtcA complexes during their initial response to nitrogen starvation or the impact of a PipX point mutation on the activity of PipX-PII and PipX-NtcA reporters are further indications of the sensitivity of the system. This study reveals additional regulatory complexities in the PipX interaction network, opening a path for future research on cyanobacteria.

Interoceptive posture awareness and accuracy: a novel photographic strategy towards making posture actionable.

Interoception, sometimes referred to as the 'hidden sense,' communicates the state of internal conditions for autonomic energy regulation and is important for human motor control as well as self-awareness. The insula, the cortex of interoception, integrates internal senses such as hunger, thirst and emotions. With input from the cerebellum and proprioceptive inputs, it creates a vast sensorimotor network essential for static posture and dynamic movement. With humans being bipedal to allow for improved mobility and energy utilization, greater neuromotor control is required to effectively stabilize and control the four postural zones of mass (i.e., head, torso, pelvis, and lower extremities) over the base of support. In a dynamic state, this neuromotor control that maintains verticality is critical, challenging energy management for somatic motor control as well as visceral and autonomic functions. In this perspective article, the authors promote a simple series of posture photographs to allow one to integrate more accurate alignment of their postural zones of mass with respect to the gravity line by correlating cortical interoception with cognitive feedback. Doing this focuses one on their body perception in space compared to the objective images. Strengthening interoceptive postural awareness can shift the net result of each zone of postural mass during day-to-day movement towards stronger posture biomechanics and can serve as an individualized strategy to optimize function, longevity, and rehabilitation.

Dual glucagon-like peptide-1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity.

AIMS: To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies. MATERIALS AND METHODS: We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 µg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE). RESULTS: A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry. CONCLUSION: Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE.

Bardet-Biedl syndrome: A clinical overview focusing on diagnosis, outcomes and best-practice management.

Bardet-Biedl syndrome (BBS) is a genetic disorder characterized by early-onset obesity, polydactyly, genital and kidney anomalies, developmental delay and vision loss due to rod-cone dystrophy. BBS is an autosomal recessive disorder with >20 implicated genes. The genotype-phenotype relationship in BBS is not clear, and there may be additional modifying factors. The underlying mechanism is dysfunction of primary cilia. In BBS, receptor trafficking in and out of the cilia is compromised, affecting multiple organ systems. Along with early-onset obesity, hyperphagia is a prominent symptom and contributes significantly to clinical morbidity and caregiver burden. While there is no cure for BBS, setmelanotide is a new pharmacotherapy approved for treatment of obesity in BBS. The differential diagnosis for BBS includes other ciliopathies, such as Alstrom syndrome, and other genetic obesity syndromes, such as Prader-Willi syndrome. Careful clinical history and genetic testing can help determine the diagnosis and a multidisciplinary team is necessary to guide clinical management.

Hypothalamic control of body fat mass by food intake: The key to understanding why obesity should be treated as a disease.

BACKGROUND: Hypothalamic centres have been recognized to play a central role in body weight regulation for nearly 70 years. AIMS: In this review, we will explore the current undersanding of the role the hypothalamus plays in controlling food intake behaviours. MATERIALS AND METHODS: Review of relevant literature from PubMed searches and review article citations. RESULTS: Beginning with autopsy studies showing destructive hypothalamic lesions in patients manifesting hyperphagia and rapid weight gain, followed by animal lesioning studies pinpointing adjacent hypothalamic sites as the 'satiety' centre and the 'feeding' centre of the brain, the neurocircuitry that governs our body weight is now understood to consist of a complex, interconnected network, including the hypothalamus and extending to cortical sites, reward centres and brainstem. Neurons in these sites receive afferent signals from the gastrointestinal tract and adipose tissue indicating food availability, calorie content, as well as body fat mass. DISCUSSION: Integration of these complex signals leads to modulation of the two prime effector systems that defend a body fat mass set point: food intake and energy expenditure. CONCLUSION: Understanding the hypothalamic control of food intake forms the foundation for understanding and managing obesity as a chronic disease.

Polyphosphate kinase deletion increases laboratory productivity in cyanobacteria.

Identification and manipulation of cellular energy regulation mechanisms may be a strategy to increase productivity in photosynthetic organisms. This work tests the hypothesis that polyphosphate synthesis and degradation play a role in energy management by storing or dissipating energy in the form of ATP. A polyphosphate kinase (ppk) knock-out strain unable to synthesize polyphosphate was generated in the cyanobacterium Synechocystis sp. PCC 6803. This mutant strain demonstrated higher ATP levels and faster growth than the wildtype strain in high-carbon conditions and had a growth defect under multiple stress conditions. In a strain that combined ppk deletion with heterologous expression of ethylene-forming enzyme, higher ethylene productivity was observed than in the wildtype background. These results support the role of polyphosphate synthesis and degradation as an energy regulation mechanism and suggest that such mechanisms may be effective targets in biocontainment design.

Effect of osteopathic manipulative treatment and Bio-Electro-Magnetic Energy Regulation (BEMER) therapy on generalized musculoskeletal neck pain in adults.

CONTEXT: General neck pain is a prevalent complaint made by patients to their physicians and is often of a suspected musculoskeletal origin. Osteopathic manipulative treatment (OMT) is a form of manual therapy utilized by osteopathic physicians and some allopathic physicians to treat a broad variety of musculoskeletal ailments, including neck pain. Bio-Electro-Magnetic Energy Regulation (BEMER) is an emerging therapeutic modality that deploys a biorhythmically defined stimulus through a pulsed electromagnetic field and has been shown to reduce musculoskeletal pain. Studies on these treatments have independently yielded promising results. Therefore, it is possible that the utility of OMT and BEMER can produce an additive improvement in the treatment of neck pain. OBJECTIVES: The objectives of this study are to investigate the individual and combined effects of OMT and BEMER therapy on neck pain in adults. METHODS: Adults with nonspecific neck pain were recruited for the study. A total of 44 participants met the study inclusion criteria and were randomized into one of four study groups: OMT-only, BEMER-only, OMT+BEMER, or CONTROL (light touch and sham). Forty subjects completed the study, and data for 38 participants were included in our analyses. An OMT and BEMER protocol were specifically designed for this study under the guidance of a licensed osteopathic physician. Participants underwent intervention for a duration of 3 weeks. Data were obtained through baseline and postintervention assessments utilizing three surveys: Neck Disability Index (NDI), Visual Analog Scale (VAS), and Short Form 12-item Health Survey (SF-12, divided into Mental and Physical). One-way analysis of variance (ANOVA) analysis was performed retrospectively on pre- and postintervention absolute means between study groups. Significance was set at p<0.05. RESULTS: One-way ANOVA analysis demonstrated a statistically significant difference in pre- vs. postintervention mean scores between BEMER and CONTROL (p<0.05), BEMER compared to OMT (p<0.005), and BEMER compared to BEMER+OMT (p<0.05), in the NDI. The OMT+BEMER group reported an average reduction in pain on the VAS of 21.3 (±29.3) points, or a 65.0 % reduction of pain. A similarly substantial decrease in pain was reported in the BEMER study group, which showed a 46.2 % reduction in pain from baseline. The OMT and CONTROL study groups only reported a 2.9 and 23.9 % decrease, respectively. The BEMER and OMT+BEMER study groups also demonstrated a reduction in subjective reporting on the NDI, by 53.8 and 26.3 %, respectively. The BEMER study group also achieved the most substantial improvement in mental and physical well-being as reported by the SF-12. CONCLUSIONS: Study arms that incorporated BEMER yielded improvements on the NDI, VAS, and SF-12, indicating benefits to BEMER regarding improved overall functionality in routine daily activities as well as a reduction in nonspecific neck pain. Perceived pain, as demonstrated on the VAS, was seemingly improved in an additive fashion from the BEMER group to the OMT+BEMER group, although the results did not achieve statistical significance. Further study with greater participation could provide additional insight.

No evidence of compensatory changes in energy balance, despite reductions in body weight and liver fat, during dapagliflozin treatment in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled, cross-over trial (ENERGIZE).

AIM: This study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)-determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: Patients were given dapagliflozin 10 mg once daily in a randomized, double-blind, placebo-controlled trial with short-term (1 week) and long-term (12 weeks) cross-over periods. The primary outcome was the difference in test meal food intake between long-term dapagliflozin and placebo treatment. Secondary outcomes included short-term differences in test meal food intake, short- and long-term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1 H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI). RESULTS: In total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2 , glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91-16.27, p = .004], and body weight (-2.84 vs. -0.87 kg) versus placebo. There was no short- or long-term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI -127.9 to 139.3, p = .933); 15.8 g (95% CI -147.7 to 116.1, p = .813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction -4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin. CONCLUSIONS: The reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure.

Energy constraint and compensation: Insights from endurance athletes.

The Constrained Model of Total Energy Expenditure predicts that increased physical activity may not influence total energy expenditure, but instead, induces compensatory energetic savings in other processes. Much remains unknown, however, about concepts of energy expenditure, constraint and compensation in different populations, and it is unclear whether this model applies to endurance athletes, who expend very large amounts of energy during training and competition. Furthermore, it is well-established that some endurance athletes consciously or unconsciously fail to meet their energy requirements via adequate food intake, thus exacerbating the extent of energetic stress that they experience. Within this review we A) Describe unique characteristics of endurance athletes that render them a useful model to investigate energy constraints and compensations, B) Consider the factors that may combine to constrain activity and total energy expenditure, and C) Describe compensations that occur when activity energy expenditure is high and unmet by adequate energy intake. Our main conclusions are as follows: A) Higher activity levels, as observed in endurance athletes, may indeed increase total energy expenditure, albeit to a lesser degree than may be predicted by an additive model, given that some compensation is likely to occur; B) That while a range of factors may combine to constrain sustained high activity levels, the ability to ingest, digest, absorb and deliver sufficient calories from food to the working muscle is likely the primary determinant in most situations and C) That energetic compensation that occurs in the face of high activity expenditure may be primarily driven by low energy availability i.e., the amount of energy available for all biological processes after the demands of exercise have been met, and not by activity expenditure per se.

Impact of Oats on Appetite Hormones and Body Weight Management: A Review.

PURPOSE OF REVIEW: This study aims to review the hunger hormones in obesity management and the impact of oats in regulating these hormones for hunger suppression and body weight management. In this review, the impact of various edible forms of oats like whole, naked, sprouted, or supplemented has been investigated for their appetite hormones regulation and weight management. RECENT FINDINGS: The onset of obesity has been greatly associated with the appetite-regulating hormones that control, regulate, and suppress hunger, satiety, or energy expenditure. Many observational and clinical studies prove that oats have a positive effect on anthropometric measures like BMI, waist circumference, waist-to-hip ratio, lipid profile, total cholesterol, weight, appetite, and blood pressure. Many studies support the concept that oats are rich in protein, fiber, healthy fats, Fe, Zn, Mg, Mn, free phenolics, ß-glucan, ferulic acid, avenanthramides, and many more. Beta-glucan is the most important bioactive component that lowers cholesterol levels and supports the defense system of the body to prevent infections. Hence, several clinical studies supported oats utilization against obesity, appetite hormones, and energy regulation but still, some studies have shown no or little significance on appetite. Results of various studies revealed the therapeutic potentials of oats for body weight management, appetite control, strengthening the immune system, lowering serum cholesterol, and gut microbiota promotion by increased production of short-chain fatty acids.

Validation of accelerometer placement to capture energy expenditure using doubly labeled water.

This study compared accelerometer-measured physical activity by body placement to daily total energy expenditure (TEE) and activity energy expenditure (AEE) measured using doubly labeled water (DLW). Forty-nine adult participants wore accelerometers placed on the nondominant wrist, dominant wrist, and chest while also undergoing DLW assessments. In adjusted models, wrist-measured physical activity (p < 0.05), but not chest-measured physical activity (p > 0.05), was associated with TEE and AEE and explained a significant amount of variance that was not explained by age, sex, height, or body composition (R2 change = 0.04-0.08; all p < 0.05). Accelerometer placement location is an important consideration when using accelerometry to provide information about energy expenditure.

Spexin and Galanin in Metabolic Functions and Social Behaviors With a Focus on Non-Mammalian Vertebrates.

Spexin (SPX) and galanin (GAL) are two neuropeptides that are phylogenetically related and have descended from a common ancestral gene. Considerable attention has been given to these two multifunctional neuropeptides because they share GAL receptors 1,2, and 3. Since GAL and SPX-synthesizing neurons have been detected in several brain areas, therefore, it can be speculated that SPX and GAL are involved in various neurophysiological functions. Several studies have shown the functions of these two neuropeptides in energy regulation, reproduction, and response to stress. SPX acts as a satiety factor to suppress food intake, while GAL has the opposite effect as an orexigenic factor. There is evidence that SPX acts as an inhibitor of reproductive functions by suppressing gonadotropin release, while GAL modulates the activity of gonadotropin-releasing hormone (GnRH) neurons in the brain and gonadotropic cells in the pituitary. SPX and GAL are responsive to stress. Furthermore, SPX can act as an anxiolytic factor, while GAL exerts anti-depressant and pro-depressive effects depending on the receptor it binds. This review describes evidence supporting the central roles of SPX and GAL neuropeptides in energy balance, reproduction, stress, and social behaviors, with a particular focus on non-mammalian vertebrate systems.

Daily variability in mothers' and fathers' feeding practices and associations with children's eating behaviors.

The current study explores daily variability in maternal and paternal pressuring, restrictive, and structure-related feeding practices and their associations with child energy regulation and food refusal. Multilevel models were run separately for mothers and fathers to understand these associations, as well as within a dyadic framework to account for the interdependence of partners. One hundred families with at least one child between 3- to 5-years old participated by completing seven days of daily diaries. Results suggest there is daily variability in feeding practices for mothers and fathers and children's energy regulation and food refusal. Mothers' daily reports (within family variability) suggested that on days when mothers used more pressure and less structure than usual, children showed more food refusal. Fathers' daily reports suggested that on days when fathers used more pressure or less structure, children showed less energy regulation. On average across the week (between family variability), maternal pressure and restriction was related to child energy regulation. Dyadic multilevel models suggested that fathers' daily feeding behavior was associated with child eating behavior, while mothers' pressure and restrictive feeding on average across the week was a better predictor of between family variability in child eating behavior. For provision of support or structure during feeding, maternal structure was related to less father-reported energy regulation and paternal structure was related to more father-reported energy regulation. The results highlight the necessity of considering both mothers' and fathers' behaviors from day-to-day to get a more authentic picture of the family feeding relationship.

Substrate-free, ultra-conformable PEDOT: PSS E-tattoo achieved by energy regulation on skin.

Electronic tattoo has great potential application in mobile health. Fully conformal contact between E-tattoo and skin is critical for reliable monitoring. In this paper, we reported a substrate-free, ultra-conformable PEDOT: PSS (3,4-ethylenedioxythiophene):poly(styrene-sulfonate) E-tattoo achieved by interface energy regulation on skin. The controllable gel/dry electrode mutual transformation property of PEDOT: PSS was carefully studied and reported. Then a novel transfer approach was studied to transfer thin, substrate-free PEDOT: PSS E-tattoo onto skin. Meanwhile, PEDOT: PSS E-tattoo was gelled, then dried directly on skin, regulating its bending energy, contact area, and interface adhesion energy with skin. Through this method, the critical thickness of the after-transformation dry E-tattoo that could form fully conformal contact with skin was increased by 4 times. The electrode-skin interface impedance and ECG measurement performance of the reported E-tattoo were on par with commercial Ag/AgCl gel electrodes, while offering superior comfort and reliability. The substrate-free, ultra-conformable PEDOT: PSS E-tattoo could be applied as sensing electrode for reliable monitoring in mobile health.

Exercise in People With Cancer: A Spotlight on Energy Regulation and Cachexia.

Exercise is increasingly becoming a standard of cancer care, with well-documented benefits for patients including improved mental wellbeing and reduced treatment-related side effects. However, important gaps in knowledge remain about how to optimise exercise prescription for people with cancer. Importantly, it remains unclear how exercise affects the progression of cancer cachexia (a wasting disease stemming from energy imbalance, and a common manifestation of advanced malignant disease), particularly once the condition has already developed. It was recently suggested that the anti-tumour effect of exercise might come from improved energetic capacity. Here, we highlight the possible effect of exercise on energetic capacity and energy regulation in the context of cancer, and how this might affect the progression of cancer cachexia. We suggest that due to the additional energy demand caused by the tumour and associated systemic inflammation, overreaching may occur more easily in people with cancer. Importantly, this could result in impaired anti-tumour immunity and/or the exacerbation of cancer cachexia. This highlights the importance of individualised exercise programs for people with cancer, with special consideration for the regulation of energy balance, ongoing monitoring and possible nutritional supplementation to support the increased energy demand caused by exercise.

Effects of a Bio-Electromagnetic Energy Regulation Blanket on Thoracolumbar Epaxial Muscle Pain in Horses.

Back pain and inflammation of the epaxial musculature is a significant problem in all equine athletes. Treatment of back pain can be challenging and often requires a multimodal approach. In humans, bio-electromagnetic energy regulation therapy (BEMER) has been reported to be effective in pain modulation. With its increased use in people comes a similar robust application in veterinary medicine unfortunately, there is unsubstantiated evidence for this type of therapy in horses. Objectives of this study were to assess analgesic responses and biomechanical outcome variables using a bio-electromagnetic energy regulation therapy blanket, and to evaluate serum biomarkers as a method to monitor the treatment effects in horses with thoracolumbar epaxial muscle pain. Cohort study of 8 horses treated for 3 consecutive days. Horses with naturally-occurring thoracolumbar epaxial muscle pain were used in this study. Objective outcome variables were recorded daily for 5 days, which included spinal evaluation, mechanical nociceptive thresholds, electromyography, kinematics, kinetics, and serum biomarkers. BEMER blanket therapy significantly improved thoracolumbar epaxial muscle nociceptive thresholds. Center of pressure displacement as a measure of postural stability was significantly improved as well as significant gains in spinal flexibility were demonstrated at study completion. A significant treatment effect was not appreciated in measures of muscle tone, ground reaction forces or serum biomarkers. Limitations include the lack of a control group and a definitive structural diagnosis of thoracolumbar epaxial muscle pain. The BEMER blanket produced significant clinical and biomechanical effects in horses with back pain.

A novel hypothesis linking low-grade ketonaemia to cardio-renal benefits with sodium-glucose cotransporter-2 inhibitors.

The cardio-renal benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors are well established. In 2016, we postulated that these benefits are attributable, in part, to the occurrence of chronic low-grade ketonaemia and a shift in myocardial and renal fuel metabolism away from fat oxidation, which is energy inefficient, towards ketone oxidation, which is more energy efficient. This shift improves myocardial and renal function and can potentially translate into lower rates of progression to heart failure and end-stage kidney disease in patients with and without diabetes. There is now evidence that, in addition to being an efficient fuel substrate, ketones also have antiinflammatory and antioxidative benefits on the heart and the kidney. In addition, ketones have positive effects on mitochondrial biogenesis and function, and on erythropoiesis, and thereby are potentially able to further ameliorate the proinflammatory and hypoxic milieu in those with heart and kidney failure, independent of hyperglycaemia. In the present review, we propose a novel hypothesis to link the pleiotropic effects of low-grade ketonaemia to the cardio-renal benefits seen with SGLT2 inhibitors.

Antiobesity therapeutics with complementary dual-agonist activities at glucagon and glucagon-like peptide 1 receptors.

AIM: To develop more effective and long-lasting antiobesity and antidiabetic therapeutics by employing novel chemical modifications of glucagon-like peptide-1 receptor (GLP-1R) agonists. METHODS: We constructed novel unimolecular dual agonists of GLP-1R and glucagon receptor prepared by linking sEx-4 and native glucagon (GCG) via lysine or triazole [sEx4-GCG(K) and sEx4-GCG(T), respectively] and evaluated their antiobesity and antidiabetic efficacy in the diabetic and obese mouse model. RESULTS: Both sEx4-GCG(K) and sEx4-GCG(T) showed the beneficial metabolic effects of GLP-1 and glucagon: they promoted weight loss and ameliorated insulin resistance and hepatic steatosis. They also increased thermogenesis in brown adipose tissue, and lipolysis and ß-oxidation in white adipose tissue, with concomitant suppression of lipogenesis. Furthermore, both dual agonists activated the 5'-AMP-activated protein kinase signalling pathway and prevented palmitate-induced oxidative stress in skeletal muscle cells. CONCLUSION: Through their complementary dual agonism, sEx4-GCG(T) and sEx4-GCG(K) induce more marked weight loss and metabolic improvements than conventional agonists, and could be developed as novel therapeutic agents for the treatment of obesity and associated metabolic disorders in humans.

A clinical overview of non-alcoholic fatty liver disease: A guide to diagnosis, the clinical features, and complications-What the non-specialist needs to know.

Non-alcoholic fatty liver disease (NAFLD) has a rapidly rising prevalence worldwide and is the most common cause of liver disease in developed countries. In this article, we discuss the spectrum of disease of NAFLD with a focus on the earlier spectrum of the disease that is commonly encountered by non-specialists, as well as the hepatic and extra-hepatic associations of the disease. We discuss in detail the two common presentations of NAFLD, incidentally detected hepatic steatosis and asymptomatic raised liver enzymes, and provide an algorithm for management and continued to follow up for these patients. Considerations for the management of cardiovascular comorbidities in these patients are also discussed. Finally, we cover the topic of screening for NAFLD in high-risk populations.

Macronutrient intake, appetite, food preferences and exocrine pancreas function after treatment with short- and long-acting glucagon-like peptide-1 receptor agonists in type 2 diabetes.

AIM: To clarify the distinct effects of a long-acting (liraglutide) and a short-acting (lixisenatide) glucagon-like peptide-1 receptor agonist (GLP-1 RA) on macronutrient intake, gastrointestinal side effects and pancreas function. MATERIALS AND METHODS: Fifty participants were randomized to either lixisenatide or liraglutide for a treatment period of 10 weeks. Appetite, satiety, macronutrient intake, gastrointestinal symptoms and variables related to pancreatic function and gastric emptying were assessed at baseline and after treatment. RESULTS: Both GLP-1 RAs reduced macronutrient intake similarly. Weight loss and appetite reduction were not related to the delay in gastric emptying or gastrointestinal side effects (P > .05). Lipase increased significantly with liraglutide treatment (by 18.3 ± 4.1 U/L; P = .0001), but not with lixisenatide (-1.8 ± 2.4 U/L; P = .46). Faecal elastase and serum ß-carotin levels (indicators for exocrine pancreas function) improved in both groups (P < .05). Changes in lipase activities did not correlate with gastrointestinal symptoms (P > .05 for each variable). CONCLUSIONS: Both GLP-1 RAs comparably affected body weight, energy and macronutrient intake. Both treatments were associated with indicators of improved exocrine pancreas function. Reductions in appetite and body weight as a result of treatment with short- or long-acting GLP-1 RAs are not driven by changes in gastric emptying or gastrointestinal side effects.