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.

Markers of Bone Metabolism in Obese Individuals Undergoing Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Besides its advantages, bariatric surgery implicates a risk of nutritional deficiencies, which might result in impaired bone metabolism. We assessed the effect of laparoscopic sleeve gastrectomy (LSG) on blood markers of bone metabolism in obese patients during a 3-year observation period. METHODS: In 39 obese patients (29 women, 10 men, mean BMI 51.8 ± 6.8 kg/m(2)) undergoing LSG, we measured blood concentrations of 25-hydroxyvitamin D (25(OH)D), calcium, parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and N-telopeptides crosslinks (NTx) before LSG and up to 3 years postoperatively. Vitamin D and calcium supplementations were recorded. RESULTS: LSG caused an excess weight loss (EWL) of 54 ± 20 % after 3 years. Before surgery, we found decreased levels of 25(OH)D and calcium in 80 and 5 % of the subjects, respectively, while increased levels of PTH, BAP, and NTx were found in 39, 28, and 21 %, respectively. Mean levels of NTx and the prevalence of elevated levels of NTx increased within 2 years (p < 0.001 and p < 0.01). Neither mean blood concentrations of 25(OH)D, calcium, PTH, and BAP nor relative prevalence of deficiencies regarding these markers changed during the study period. The supplementation rates of calcium and vitamin D increased postoperatively. CONCLUSIONS: Morbid obesity is associated with pronounced changes of markers of bone metabolism; LSG did neither aggravate nor ameliorate vitamin D metabolism within a 3-year time period, but led to increased bone resorption 2 years postoperatively. Routine supplementation of calcium and vitamin D is not likely sufficient to compensate the obesity-associated deficiencies in bone metabolism.