Atrial natriuretic peptide and leptin interactions in healthy men.

Introduction: Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans in vivo. Methods: Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial. Results: Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion in vivo, indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release. Discussion: The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under DRKS00024559).

Competing influences on healthy food choices: Mindsetting versus contextual food cues.

Food choices are influenced by one's current mindset, suggesting that supporting health (vs. a palatability) mindsets could improve daily food choices. The question rises, however, to what extent internal mindsets still guide choices when people are exposed to external food-context stimuli in an obesogenic environment. To examine these two competing effects we induced health vs. palatability mindsets, and investigated the robustness of the mindset effect by presenting food-context stimuli during a Pavlovian-to-Instrumental-Transfer (PIT) task in two separate cohorts of 102 (76 females) Dutch and 120 (60 females) German participants. For the mindset induction, participants rated food items on visual analogue scales (VAS), based on healthiness and palatability, respectively. In each cohort, half of the participants received a health, the other half a palatability mindset induction. Additionally, we explored whether 'mindset triggers' could be used to further shape behavior. Triggers were established by placing unfamiliar logos at the extreme ends of the VASs used for the mindset inductions. Independent of the mindset, food-associated stimuli influenced food choices in accordance with the previously learned association in each test phase. Health mindset induction biased food choices towards healthier, palatability mindset towards unhealthier choices in the first cohort, but not in the second. The mindset triggers had a more robust effect. These induced healthier (triggers for healthy and not-palatable) and unhealthier (triggers for unhealthy and palatable) food choices in both cohorts alike. Interestingly, these effects did not tamper with the overall effect of Pavlovian cues and were thus true in the presence and absence of food-context stimuli. Therefore, we show that, in our experimental setting, food-associated mindset triggers can be used to bias food choices towards a healthy snack even in an obesogenic environment.

Functional Connectivity Within the Gustatory Network Is Altered by Fat Content and Oral Fat Sensitivity - A Pilot Study.

Background: The amount of fat in ingested food dictates specific activation patterns in the brain, particularly in homeostatic and reward-related areas. Taste-specific brain activation changes have also been shown and the sensitivity to the oral perception of fat is associated with differential eating behavior and physiological parameters. The association between oral fat sensitivity and neuronal network functions has, however, not yet been defined. Objective: We aimed to investigate the association between fat-dependent neuronal functional connectivity patterns and oral fat sensitivity. Design: To investigate the underlying changes in network dynamics caused by fat intake, we measured resting-state functional connectivity in 11 normal-weight male participants before and after a high- vs. a low-fat meal on two separate study days. Oral fat sensitivity was also measured on both days. We used a high-resolution functional magnetic resonance imaging (MRI) sequence to measure any connectivity changes in networks with the seed in the brainstem (nucleus tractus solitarii, NTS), in homeostatic (hypothalamus) and in reward regions (ventral and dorsal striatum). Seed-based functional connectivity (FC) maps were analyzed using factorial analyses and correlation analyses with oral fat sensitivity were also performed. Results: Regardless of fat content, FC between NTS and reward and gustatory areas was lower after ingestion. Oral fat sensitivity was positively correlated with FC between homeostatic regions and limbic areas in the high-fat condition, but negatively correlated with FC between the dorsal striatum and somatosensory regions in the low-fat condition. Conclusion: Our results show the interaction of oral fat sensitivity with the network based neuronal processing of high- vs. low-fat meals. Variations in neuronal connectivity network patterns might therefore be a possible moderator of the association of oral fat sensitivity and eating behavior.

Leptin Is Not Essential for Obesity-Associated Hypertension.

BACKGROUND AND OBJECTIVE: Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution. SUBJECTS AND METHODS: To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2-7 days and 7-14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene. RESULTS: Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031). CONCLUSIONS: These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone.

Leptin Replacement Reestablishes Brain Insulin Action in the Hypothalamus in Congenital Leptin Deficiency.

OBJECTIVE: Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral metabolism. RESEARCH DESIGN AND METHODS: In a leptin-deficient patient, we investigated the impact of leptin substitution on central insulin action, as quantified by changes in neuronal activity after intranasal insulin application. This was assessed before and during the first year of metreleptin substitution. RESULTS: After only 1 year, treatment with metreleptin reestablishes brain insulin sensitivity, particularly in the hypothalamus and, to a lesser degree, in the prefrontal cortex. Results are depicted in comparison with a control group. In our patient, brain activation changes were accompanied by substantial weight loss, reduced visceral adipose tissue, reduced intrahepatic lipid content, and improved whole-body insulin sensitivity. CONCLUSIONS: Leptin replacement and weight loss improved homeostatic insulin action in the patient in question.

Detection thresholds for four different fatty stimuli are associated with increased dietary intake of processed high-caloric food.

BMI-specific differences in food choice and energy intake have been suggested to modulate taste perception. However, associations between body composition and fat taste sensitivity are controversial. The objective of this study was to examine the association between body composition, dietary intake and detection thresholds of four fatty stimuli (oleic acid, paraffin oil, canola oil, and canola oil spiked with oleic acid) that could be perceived via gustatory and/or textural cues. In 30 participants, fat detection thresholds were determined in a repeated measurements design over twelve days. Weight status was examined by measuring the participants' BMI, waist circumference and waist-to-hip ratio. The habitual food intake was assessed via several questionnaires and twelve, non-consecutive 24-hour food diaries. In this study, a negative correlation was found between fat detection thresholds and the intake of food rich in vitamins and fibre. Moreover, a positive correlation was identified between the intake of high-fat food and fat detection thresholds. No differences in fat detection thresholds were observed due to variations in BMI or waist-to-hip ratio. These findings indicate that a regular intake of fatty foods might decrease an individuals' perceptual response to fats which might lead to excess fat intake on the long term.

Oil Perception-Detection Thresholds for Varying Fatty Stimuli and Inter-individual Differences.

Multiple lines of research have demonstrated that humans can perceive fat in the form of free fatty acids (FFAs). However, the dietary concentration of FFAs is generally very low and fat is mainly consumed as triacylglycerol (TAG). The aim of this study was to examine the perception of different fatty stimuli and possible associations between them. Therefore, detection thresholds for 4 fatty stimuli (oleic acid [FFA], paraffin oil [mixture of hydrocarbon molecules], canola oil [TAG-rich], and canola oil spiked with oleic acid [rich in TAGs and FFAs]) were determined in 30 healthy participants. Additionally, inter-individual differences in fat perception were examined. It was observed that oleic acid was perceivable at significantly lower concentrations than all other stimuli (P < 0.001). Similarly, canola oil with oleic acid was detectable at lower concentrations than canola oil alone (P < 0.001). Moreover, canola oil detection thresholds were significantly lower than paraffin oil detection thresholds (P = 0.017). Participants who were sensitive for low concentrations for oleic acid showed lower detection thresholds for canola oil with and without oleic acid, compared with participants that were less sensitive for oleic acid. The results of this study demonstrate that the higher the concentrations of FFAs in the stimuli, the lower the individual fat detection threshold. Moreover, participants being sensitive for lower concentrations of FFAs are also more likely to detect low concentrations of TAG-rich fats as it is found in the human diet.