High cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention

Tschritter, Otto; Preißl, Hubert; Hennige, Anita M.; Sartorius, Tina; Štingl, Katarína; Heni, Martin; Ketterer, Caroline; Stefan, Norbert; Machann, Jürgen; Schleicher, Erwin; Fritsche, Andreas; Häring, Hans‐Ulrich

doi:10.1007/s00125-011-2309-z

Cited by 58 publications

(50 citation statements)

References 21 publications

(29 reference statements)

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“…Thus, participants with higher visceral fat content reveal a diminished hypothalamic response to insulin, indicating a relationship between cerebral insulin resistance and metabolically unfavorable abdominal adiposity (23). Indeed, during the course of a lifestyle intervention study, individuals with high cerebral insulin sensitivity displayed more loss of visceral fat than those who were brain insulin resistant (24). According to these findings, we speculate that soluble factors like fatty acids derived from visceral fat may cause cerebral insulin resistance, which then may aggravate hypothalamic dysfunction, resulting in a vicious cycle.…”

Section: Discussionmentioning

confidence: 99%

Selective Insulin Resistance in Homeostatic and Cognitive Control Brain Areas in Overweight and Obese Adults

et al. 2015

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OBJECTIVEImpaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. RESEARCH DESIGN AND METHODSIn 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. RESULTSIn response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. CONCLUSIONSBrain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior.

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Section: Discussionmentioning

confidence: 99%

Selective Insulin Resistance in Homeostatic and Cognitive Control Brain Areas in Overweight and Obese Adults

et al. 2015

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“…In addition to various other functions, such as memory and reward, insulin delivery to the brain induced weight loss [29,50]. Brain insulin sensitivity even predicts loss of metabolically unhealthy visceral fat during a lifestyle intervention [51]. Furthermore, insulin in the brain was recently shown to modulate peripheral insulin sensitivity in humans [28,29].…”

Section: Discussionmentioning

confidence: 99%

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity

et al. 2016

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Aims/hypothesis Variations in FTO are the strongest common genetic determinants of adiposity, and may partly act by influencing dopaminergic signalling in the brain leading to altered reward processing that promotes increased food intake. Therefore, we investigated the impact of such an interaction on body composition, and peripheral and brain insulin sensitivity. Methods Participants from the Tübingen Family study (n = 2245) and the Malmö Diet and Cancer study (n = 2921) were genotyped for FTO SNP rs8050136 and ANKK1 SNP rs1800497. Insulin sensitivity in the caudate nucleus, an important reward area in the brain, was assessed by fMRI in 45 participants combined with intranasal insulin administration. Results We found evidence of an interaction between variations in FTO and an ANKK1 polymorphism that associates with dopamine (D2) receptor density. In cases of reduced D2 receptor availability, as indicated by the ANKK1 polymorphism, FTO variation was associated with increased body fat and waist circumference and reduced peripheral insulin sensitivity. Similarly, altered central insulin sensitivity was observed in the caudate nucleus in individuals with the FTO obesity-risk allele and diminished D2 receptors. Conclusions/interpretation The effects of variations in FTO are dependent on dopamine D2 receptor density (determined by the ANKK1 polymorphism). Carriers of both risk alleles might, therefore, be at increased risk of obesity and diabetes.

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“…Thus, the good health status of our elderly participants, as verified by clinical examination and evidenced by their merely moderately elevated body weight in comparison to our young subjects, might have ensured sufficient potency of the insulin signal. Vice versa, indicators of high cerebral insulin sensitivity have been found to be associated with successful loss of body fat during lifestyle intervention (Tschritter et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Central nervous insulin administration before nocturnal sleep decreases breakfast intake in healthy young and elderly subjects

Santiago

Hallschmid

2017

Diabetologie und Stoffwechsel

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Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m 2 ) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m 2 ) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin delivery that extends across sleep and might be of particular relevance for potential therapeutic applications.

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High cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention

Cited by 58 publications

References 21 publications

Selective Insulin Resistance in Homeostatic and Cognitive Control Brain Areas in Overweight and Obese Adults

Selective Insulin Resistance in Homeostatic and Cognitive Control Brain Areas in Overweight and Obese Adults

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity

Central nervous insulin administration before nocturnal sleep decreases breakfast intake in healthy young and elderly subjects

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