Central insulin modulates dopamine signaling in the human striatum

2021 ◽  
Author(s):  
Stephanie Kullmann ◽  
Dominik Blum ◽  
Benjamin Assad Jaghutriz ◽  
Christoph Gassenmaier ◽  
Benjamin Bender ◽  
...  
Keyword(s):  
Body Weight ◽  
Functional Connectivity ◽  
Resting State ◽  
Normal Weight ◽  
Dopamine Neurons ◽  
Whole Body ◽  
Binding Potential ◽  
Intranasal Insulin ◽  
Dopamine Signaling ◽  
Whole Body Metabolism

Abstract Objective Activity in the dopaminergic pathways of the brain is highly sensitive to body weight and metabolic states. Animal studies show that dopamine neurons are important targets for the metabolic hormone insulin with abolished effects in the insulin resistant state, leading to increases in body weight and food intake. In humans, the influence of central acting insulin on dopamine and effects of their interplay are still elusive. Research Design and Methods We investigated whether central administered insulin influences dopaminergic activity in striatal regions and whole-brain neural activity. Using a PET/MRI hybrid scanner, we simultaneously performed [ 11C]-raclopride-PET and resting state fMRI in 10 healthy normal weight men after application of intranasal insulin or placebo on two separate days in a randomized, placebo-controlled, blinded, crossover trial. Results In response to central insulin compared to placebo administration, we observed greater [ 11C]-raclopride binding potential (BPnd) in the bilateral ventral and dorsal striatum. This suggests an insulin-induced reduction in synaptic dopamine levels. Resting-state striatal activity was lower 15 and 30 min after nasal insulin compared to placebo. Functional connectivity of the mesocorticolimbic circuitry associated with differences in dopamine levels: individuals with a stronger insulin-induced effect on dopamine levels showed a stronger increase in functional connectivity 45 min after intranasal insulin. Conclusions This study indicates that central insulin modulates dopaminergic tone in the striatum, which may affect regional brain activity and connectivity. Our results deepen the understanding of the insulin-dopamine interaction and the complex network that underlies the regulation of whole-body metabolism.

scholarly journals Intranasal Insulin Enhanced Resting-State Functional Connectivity of Hippocampal Regions in Type 2 Diabetes

Diabetes ◽  
2014 ◽  
Vol 64 (3) ◽  
pp. 1025-1034 ◽  
Author(s):  
Hui Zhang ◽  
Ying Hao ◽  
Bradley Manor ◽  
Peter Novak ◽  
William Milberg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Functional Connectivity ◽  
Resting State ◽  
Intranasal Insulin ◽  
Resting State Functional Connectivity

Whole Body Protein Turnover in Chronically Undernourished Individuals

1994 ◽  
Vol 86 (4) ◽  
pp. 441-446 ◽  
Author(s):  
M. J. Soares ◽  
L. S. Piers ◽  
P. S. Shetty ◽  
A. A. Jackson ◽  
J. C. Waterlow
Keyword(s):  
Body Weight ◽  
Protein Synthesis ◽  
Metabolic Rate ◽  
Muscle Mass ◽  
Basal Metabolic Rate ◽  
Normal Weight ◽  
Fat Free Mass ◽  
Whole Body ◽  
Body Protein ◽  
Chronic Undernutrition

1. Two groups of adult men were studied in Bangalore, India, under identical conditions: the ‘normal weight’ subjects (mean body mass index 20.8 kg/m2) were medical students of the institute with access to habitual energy and protein intakes ad libitum. The other group, designated ‘undernourished’, were labourers on daily wages (mean body mass index 16.7 kg/m2). 2. In an earlier study we obtained lower absolute values for both basal metabolic rate and protein synthesis in the undernourished subjects; however, when the data were expressed on a body weight or fat-free mass basis, a trend towards higher rates of protein synthesis, as well as higher basal metabolic rate, was evident. The suggestion was made that such results reflected the relatively higher energy intakes per kg body weight of the undernourished subjects on the day of study. The objective of the present study was therefore to control for the dietary intake during the measurement of whole body protein turnover. 3. In the present study dietary intakes were equated on a body weight basis; however, expressed per kg fat-free mass, the normal weight subjects had received marginally higher intakes of energy and protein. The results, however, were similar to those of the previous study. In absolute terms, basal metabolic rate, protein synthesis and breakdown were lower in the undernourished subjects. When expressed per kg body weight or per kg fat-free mass, the undernourished subjects had higher basal metabolic rates than the well-nourished subjects, whereas no differences were seen in the rate of protein synthesis or breakdown. 4. Estimates of muscle mass, based on creatinine excretion, indicated that the undernourished subjects had a higher proportion of non-muscle to muscle mass. Nitrogen flux (Q) was determined from 15N abundance in two end products, urea (Qu) and ammonia (Qa). The ratio Qu/Qa was increased in the undernourished subjects and was significantly correlated with the ratio of non-muscle to muscle mass (r = 0.81; P < 0.005). These results fit in with our earlier suggestion of a greater proportion of non-muscle (visceral) mass in undernourished subjects. 5. The present data suggest that there are no changes in the rate of protein synthesis or breakdown in chronic undernutrition when results are expressed, conventionally, per kg fat-free mass. It can be theoretically shown, however, that there could be a 15% reduction in the rate of turnover of the visceral tissues in chronic undernutrition. This, together with the reduced urinary nitrogen excretion, would contribute to nitrogen economy in these individuals.

Characterizing impulsivity and resting‐state functional connectivity in normal‐weight binge eaters

2019 ◽  
Vol 53 (3) ◽  
pp. 478-488 ◽  
Author(s):  
Rossella Oliva ◽  
Filip Morys ◽  
Annette Horstmann ◽  
Umberto Castiello ◽  
Chiara Begliomini
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Normal Weight ◽  
Resting State Functional Connectivity ◽  
Binge Eaters

scholarly journals Whole-body metabolism of glucose and lactate in productive sheep and cows

1983 ◽  
Vol 50 (2) ◽  
pp. 249-265 ◽  
Author(s):  
G. D. Baird ◽  
J. G. Van Der Walt ◽  
E. N. Bergman
Keyword(s):  
Body Weight ◽  
Dairy Cows ◽  
De Novo ◽  
Late Pregnancy ◽  
Whole Body ◽  
Early Lactation ◽  
Metabolic Pattern ◽  
Lactating Cows ◽  
Lactate Turnover ◽  
Whole Body Metabolism

1. Constant infusions of D-[U-14C]glucose, D-[6−3H]glucose and L-[U-14C]lactate were used to determine rates of apparent turnover, de novo production, disposal and interconversions of glucose and lactate, together with total recycling of glucose-C, in ewes and dairy cows during late pregnancy and early lactation. The cows were also examined while being fasted. In the fed animals, infusions were made within 5 h after the morning meal when steady-state conditions appeared to exist.2. In the ewes, circulating concentrations of glucose and lactate, and magnitudes of apparent turnovers of glucose and lactate, tended to be higher during lactation than during pregnancy, while the extent of interconversions of glucose and lactate tended to be lower.3. Although the metabolic pattern seen in the cows appeared to be similar to that of the ewes during pregnancy, there were clear differences during lactation. Thus, in the lactating cows, as compared with the lactating ewes, circulating concentrations of glucose and lactate were lower, as was apparent lactate turnover related to metabolic body-weight. Furthermore, the percentage of lactate turnover converted to glucose was higher.4. In the cows, fasting was characterized by low rates of apparent turnover of glucose and lactate and relatively high rates of interconversion of the two compounds.5. The results indicated that, under the conditions used in this study and when feeding is to recommended levels, carbohydrate metabolism in ewes is more precarious during late pregnancy than during early lactation, while in dairy cows it is more or less equally precarious in both physiological states.6. A further conclusion is that the extent of glucose–lactate interconversions, and thus Cori cycle activity, seems to be lower in ruminants than in other species.

Structural connectivity prior to whole-body sensorimotor skill learning associates with changes in resting state functional connectivity

NeuroImage ◽  
2019 ◽  
Vol 197 ◽  
pp. 191-199 ◽  
Author(s):  
Nobuaki Mizuguchi ◽  
Tom Maudrich ◽  
Rouven Kenville ◽  
Daniel Carius ◽  
Dennis Maudrich ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Structural Connectivity ◽  
Skill Learning ◽  
Whole Body ◽  
Resting State Functional Connectivity

Ventromedial hypothalamic lesions abolish compensatory reduction in energy expenditure to weight loss

1990 ◽  
Vol 258 (2) ◽  
pp. R476-R480
Author(s):  
T. R. Vilberg ◽  
R. E. Keesey
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Energy Expenditure ◽  
Weight Control ◽  
Open Circuit ◽  
Normal Weight ◽  
Female Rats ◽  
Whole Body ◽  
Behavioral Activity ◽  
Control Female

Weight loss through caloric restriction produces compensatory reductions in the whole body energy expenditure of normal rats. The present experiment determined whether rats who had become obese after ventromedial hypothalamic (VMH) lesions displayed this metabolic defense of body weight. Obese VMH-lesioned and normal-weight control female rats were assigned to one of three weight maintenance conditions (100, 90, and 80% of previously maintained body weight). Postabsorptive oxygen consumption was then measured by open-circuit respirometery while, simultaneously, behavioral activity was measured by stabilimeter. A marked decline in resting energy expenditure and behavioral activity, seen in control rats after weight loss, was absent in VMH-lesioned rats. These results suggest that VMH lesions impair the ability to adjust energy expenditure in response to alterations in nutritional status, a response that normally serves to stabilize body weight at a regulated level.

scholarly journals FTO is a transcriptional repressor to auto-regulate its own gene and potentially associated with homeostasis of body weight

2018 ◽  
Vol 11 (2) ◽  
pp. 118-132 ◽  
Author(s):  
Shu-Jing Liu ◽  
Hui-Ling Tang ◽  
Qian He ◽  
Ping Lu ◽  
Tao Fu ◽  
...  
Keyword(s):  
Body Weight ◽  
Cultured Cells ◽  
Transcriptional Repressor ◽  
Gene Promoter ◽  
Underlying Mechanism ◽  
Whole Body ◽  
Loss Of Function ◽  
Nutritional Conditions ◽  
Whole Body Metabolism ◽  
Regulatory Loop

Abstract Fat mass and obesity-associated (FTO) protein is a ferrous ion (Fe2+)/2-oxoglutarate (2-OG)-dependent demethylase preferentially catalyzing m6A sites in RNA. The FTO gene is highly expressed in the hypothalamus with fluctuation in response to various nutritional conditions, which is believed to be involved in the control of whole body metabolism. However, the underlying mechanism in response to different nutritional cues remains poorly understood. Here we show that ketogenic diet-derived ketone body β-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells. Interestingly, the FTO protein represses Fto promoter activity, which can be offset by BHB. We then demonstrate that FTO binds to its own gene promoter, and Fe2+, but not 2-OG, impedes this binding and increases FTO expression. The BHB-induced occupancy of the promoter by FTO influences the assembly of the basal transcriptional machinery. Importantly, a loss-of-function FTO mutant (I367F), which induces a lean phenotype in FTOI367F mice, exhibits augmented binding and elevated potency to repress the promoter. Furthermore, FTO fails to bind to its own promoter that promotes FTO expression in the hypothalamus of high-fat diet-induced obese and 48-h fasting mice, suggesting a disruption of the stable expression of this gene. Taken together, this study uncovers a new function of FTO as a Fe2+-sensitive transcriptional repressor dictating its own gene switch to form an auto-regulatory loop that may link with the hypothalamic control of body weight.

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo
Keyword(s):  
Metabolic Diseases ◽  
Cell Function ◽  
Whole Body ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Axis ◽  
Β Cell Function ◽  
Prevalence Of Obesity ◽  
Specific Factors ◽  
Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

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