1,721,004 research outputs found
Understanding the effect of obesity on papillary thyroid cancer: is there a need for tailored diagnostic and therapeutic management?
No full textIntroduction: Several studies have focused on the relationship between obesity and differentiated thyroid carcinoma (DTC), particularly papillary histotype (PTC). However, the association of obesity with both incidence and aggressiveness of PTC is still incompletely understood.Areas covered: We reviewed the mechanisms underlying the cross talk between obesity and thyroid carcinomas and described the most recent evidence evaluating the effect of obesity on the development of PTC, as well as the impact of excessive body weight on the clinicopathologic features and outcome of this type of cancer.Expert opinion: Available evidence suggests that excessive body weight is linked with a higher risk of getting PTC, while its impact on the aggressiveness of the disease, if present, is still not clear. Therefore, while attention should be paid to discover thyroid cancer in patients with obesity earlier, once diagnosed it should be managed following a conventional workup as in normal weight patients, based on the clinical presentation of the disease and including active surveillance if appropriate, as recommended by referral guidelines
Effects of tyrosine kinase inhibitors on thyroid function and thyroid hormone metabolism
No full textThe increasing knowledge of the molecular mechanisms in the cell signaling pathways of malignant cells, has recently led to the discovery of several tyrosine kinases (TKs), mainly TK receptors (TKR), which play a major role in the pathogenesis of many types of cancer. These receptors, physiologically involved in cell growth and angiogenesis, may harbor mutations or be overexpressed in malignant cells, and represent a target for anticancer therapy. Indeed, several therapeutic agents targeting specific altered pathways such as RET, BRAF, RAS, EGFR and VEGFR, have been identified. Tyrosine kinase inhibitors (TKIs) affect TK dependent oncogenic pathways by competing with ATP binding sites of the TK domain, thus blocking the activity of the enzyme, and thereby inhibiting the growth and spread of several cancers.
Although the therapeutic action may be very effective, these molecules, due to their mechanism of multi- targeted inhibition, may produce adverse events involving several biological systems. Both hypothyroidism and thyrotoxicosis have been reported during treatment with TKI, as well as an effect on the activity of enzymes involved in thyroid hormone metabolism. The pathogenic mechanisms leading to thyroid dysfunction and changes in serum thyroid function tests occurring in patients on TKI are reviewed and discussed in this manuscript
Endocannabinoid Anandamide Mediates the Effect of Skeletal Muscle Sphingomyelins on Human Energy Expenditure
Full text linkContext:
Skeletal muscle endocannabinoids and sphingolipids (particularly sphingomyelins) are inversely associated with sleeping energy expenditure (SLEEP) in humans. The endocannabinoid system may increase sphingolipid synthesis via cannabinoid receptor-1.
Objective:
To investigate in human skeletal muscle whether endocannabinoids are responsible for the effect of sphingomyelins on SLEEP.
Design:
Muscle endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)], endocannabinoid congeners [oleoylethanolamide (OEA), palmitoylethanolamide (PEA)], and sphingomyelin content were measured with liquid chromatography/mass spectrometry. SLEEP was assessed in a whole-room indirect calorimeter. Mediation analyses tested whether the inverse associations between sphingomyelins and SLEEP depended on endocannabinoids and endocannabinoid-related OEA and PEA.
Setting:
Inpatient study.
Participants:
Fifty-three Native Americans who are overweight.
Main Outcome Measure:
SLEEP.
Results:
AEA (r = 0.45, P = 0.001), 2-AG (r = 0.47, P = 0.0004), OEA (r = 0.27, P = 0.05), and PEA (r = 0.53, P 0.31, all P 0.05).
Conclusions:
In skeletal muscle, AEA is responsible for the sphingomyelin effect on SLEEP, indicating that endocannabinoids and sphingomyelins may jointly reduce human whole-body energy metabolism
Ketogenic Diet and Weight Loss: Is There an Effect on Energy Expenditure?
Full text linkA dysregulation between energy intake (EI) and energy expenditure (EE), the two components of the energy balance equation, is one of the mechanisms responsible for the development of obesity. Conservation of energy equilibrium is deemed a dynamic process and alterations of one component (energy intake or energy expenditure) lead to biological and/or behavioral compensatory changes in the counterpart. The interplay between energy demand and caloric intake appears designed to guarantee an adequate fuel supply in variable life contexts. In the past decades, researchers focused their attention on finding efficient strategies to fight the obesity pandemic. The ketogenic or “keto” diet (KD) gained substantial consideration as a potential weight-loss strategy, whereby the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and the activity of ketogenic enzymes. It has been hypothesized that during the first phase of KDs when glucose utilization is still prevalent, an increase in EE may occur, due to increased hepatic oxygen consumption for gluconeogenesis and for triglyceride-fatty acid recycling. Later, a decrease in 24-h EE may ensue due to the slowing of gluconeogenesis and increase in fatty acid oxidation, with a reduction of the respiratory quotient and possibly the direct action of additional hormonal signals
Urinary Dopamine Excretion Rate Decreases during Acute Dietary Protein Deprivation and Is Associated with Increased Plasma Pancreatic Polypeptide Concentration
No full textBackground: Dopamine, a key neurotransmitter in the autonomic nervous system participating in the homeostatic balance between sympathetic and parasympathetic divisions, is involved in food intake regulation. Objective: We investigated whether dopamine is altered by acute fasting or overfeeding diets with varying macronutrient content. Design: Ninety-nine healthy subjects underwent 24-h dietary interventions including eucaloric feeding, fasting, and five different overfeeding diets in a crossover design. Overfeeding diets (200% of eucaloric requirements) included one diet with 3%-protein (low-protein high-fat overfeeding—LPF: 46%-fat), three diets with 20%-protein, and a diet with 30%-protein (44%-fat). Urine was collected for 24 h and urinary dopamine concentration was quantified by high-performance liquid chromatography. Plasma pancreatic polypeptide (PP) concentration, an indirect marker of parasympathetic activity, was measured prior to and after each diet after an overnight fast. Results: During 24-h of fasting, dopamine decreased on average by ~14% compared to eucaloric conditions, whereas PP increased by two-fold (both p < 0.001). Lower dopamine during 24-h fasting correlated with increased PP (r = −0.40, p < 0.001). Similarly, on average urinary dopamine decreased during LPF by 14% (p < 0.001) and lower dopamine correlated with increased PP (r = −0.31, p = 0.01). No changes in dopamine and PP concentrations were observed during other overfeeding diets (all p > 0.05). Conclusions: Dopamine concentrations decrease during short-term fasting and overfeeding with a low-protein diet. As both dietary conditions have in common protein deficit, the correlation between dopamine and PP suggests a compensatory mechanism underlying the shift from sympathetic to parasympathetic drive during dietary protein deprivation
Reduced Albumin Concentration Predicts Weight Gain and Higher Ad Libitum Energy Intake in Humans
No full textObjective: Circulating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined.
Methods: In study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition.
Results: After adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p<0.0001). Lower albumin concentrations were associated with greater weight [β=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (β=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06).
Conclusions: Lower albumin concentrations were associated with increased ad libitum food intake and weight gain, indicating albumin as a marker of energy intake regulation
Reduced adaptive thermogenesis during acute protein-imbalanced overfeeding is a metabolic hallmark of the human thrifty phenotype
No full textBACKGROUND: The human thrifty phenotype is characterized by a greater decrease in 24-h energy expenditure (24EE) during fasting due to relatively higher eucaloric 24EE in sedentary conditions, both of which are indicative of greater propensity to weight gain. Thriftiness is also associated with a smaller increase in 24EE (i.e., reduced adaptive thermogenesis) during overfeeding. OBJECTIVES: We investigated whether short-term measures of adaptive thermogenesis during overfeeding with low/normal/high protein content characterize thriftiness. METHODS: In this secondary cross-sectional analysis of a single-arm crossover study, 24EE was measured using whole-room indirect calorimetry during energy balance, fasting, and different overfeeding conditions (low/3% protein, high/30% protein, and 3 normal/20% protein diets) with 200% of eucaloric requirements in 77 healthy individuals [63 men; BMI (in kg/m(2)): 26.4 ± 4.3; body fat by DXA: 27.7% ± 9.4%, mean ± SD] with normal glucose regulation. Relations between the 24EE during energy balance (adjusted for body composition) and 24EE during each overfeeding diet were analyzed using separate linear regression models. Participants were arbitrarily categorized as thrifty/spendthrift based on the median value (−177 kcal/d) of the difference in 24EE between fasting and energy balance conditions. RESULTS: Differences in 24EE during low/high-protein overfeeding diets (regression line slope = 0.76 and 0.68, respectively, both P 0.05 compared with slope = 1) were dependent on baseline 24EE during energy balance. Specifically, individuals with higher eucaloric 24EE (thriftier phenotype) showed smaller increases in 24EE during protein-imbalanced overfeeding. Analyzed by group, thrifty individuals had smaller increases in 24EE by 42 and 237 kcal/d during low- and high-protein overfeeding, respectively, compared with spendthrift individuals who showed greater increases in 24EE by 100 and 302 kcal/d (P ≤ 0.03 compared with thrifty group). CONCLUSIONS: During acute overfeeding conditions with low/high-protein content, thrifty participants have limited capacity to increase 24EE, indicating that impaired adaptive thermogenesis during protein-imbalanced diets further characterizes the thrifty phenotype and its susceptibility to weight gain. This trial was registered at clinicalTrials.gov as NCT00523627
Effects of short-term fasting and different overfeeding diets on thyroid hormones in healthy humans
Full text linkBackground Greater decrease in 24-h energy expenditure (EE) during fasting and smaller increase in 24-h EE during low-protein overfeeding (metabolic "thrifty" phenotype) predict weight gain. As thyroid hormones (TH) are implicated in energy intake and metabolism, we assessed whether: 1) TH concentrations are altered by 24-h fasting or overfeeding diets with varying protein content; 2) diet-related changes in TH correlate with concomitant changes in EE. Methods Fifty-eight euthyroid, healthy subjects with normal glucose regulation underwent 24-h dietary interventions including fasting, eucaloric feeding, and five overfeeding diets in a crossover design within a whole-room indirect calorimeter to measure 24-h EE. Overfeeding diets (200% of energy requirements) included three diets with 20%-protein, one diet with 3%-protein (LPF: 46%-fat), and a diet with 30%-protein (HPF: 44%-fat, n=51). Plasma free thyroxine (FT4), triiodothyronine (FT3), and fibroblast growth factor 21 (FGF21) concentrations were measured after overnight fast the morning of and after each diet. Results On average, FT4 increased by 8% (+0.09 ng/dL, 95% CI: 0.06-0.13, p<0.001) while FT3 decreased by 6% (-0.17 pg/mL, CI: -0.27 to -0.07, p=0.001) after 24-h fasting, whereas both FT4 and FT3 decreased by 5% (-0.08 ng/dL, CI: -0.11 to -0.04, p<0.0001) and 4% (-0.14 pg/mL, CI: -0.24 to -0.04, p=0.008) following HPF, respectively. Greater decreases in FT3 after HPF associated with larger decreases in FGF21 (r=0.40, p=0.005). Following LPF, mean FT3 increased by 6% (+0.14 pg/mL, CI:0.05-0.2, p=0.003) with no change in FT4 (p=0.7). No changes in TH were observed after normal-protein overfeeding diets (all p>0.1). No associations were observed between TH concentrations and diet-related changes in 24-h EE during any diet (all p>0.07). Conclusion Acute (200%), short-term (24h) changes in food intake induce small changes in TH concentrations only after diets with low (0%-fasting and 3%-protein overfeeding) or high (30%-protein overfeeding) protein content. The FT3-FGF21 association after high-protein overfeeding suggests a role for TH in inhibiting FGF21 secretion by the liver during protein excess. These results indicate that TH are involved in protein metabolism; however, they do not mediate the short-term EE response to diets that characterize the metabolic phenotypes and determine the individual susceptibility to weight gain
Urinary norepinephrine is a metabolic determinant of 24-h energy expenditure and sleeping metabolic rate in adult humans
Full text linkBACKGROUND:
Inter-individual variability in 24-hour energy expenditure (24EE) during energy balance conditions is mainly determined by differences in body composition and demographic factors. Previous studies suggested that 24EE might also be influenced by sympathetic nervous system activity via catecholamine (norepinephrine, epinephrine) secretion. Therefore, we analyzed the association between catecholamines and energy expenditure in 202 subjects from a heterogeneous population of mixed ethnicities.
METHODS:
Participants (n=202, 33% female, 14% Black, 32% Caucasian, 41% Native Americans, 11% Hispanic, age: 36.9±10.3 years (mean±SD), percentage body fat: 30.3±9.4) resided in a whole-room calorimeter over 24-h during carefully controlled energy balance conditions to measure 24EE and its components: sleeping metabolic rate (SMR), awake-fed thermogenesis (AFT), and spontaneous physical activity (SPA). Urine samples were collected, and 24-h urinary epinephrine and norepinephrine excretion rates were assessed by high-performance liquid chromatography.
RESULTS:
Both catecholamines were associated with 24EE and SMR (norepinephrine: +27 and +19 kcal/day per 10 μg/24h; epinephrine: +18 and +10 kcal/day per 1 μg/24h) in separate analyses after adjustment for age, sex, ethnicity, fat mass, fat-free mass, calorimeter room and temperature, and physical activity. In a multivariable model including both norepinephrine and epinephrine, only norepinephrine was independently associated with both 24EE and SMR (both p<0.008) while epinephrine became insignificant. Neither epinephrine nor norepinephrine were associated with adjusted AFT (both p=0.37) but epinephrine was associated with adjusted SPA (+0.5% per 1 μg/24h).
CONCLUSIONS:
Our data provide compelling evidence that sympathetic nervous system activity, mediated via norepinephrine, is a determinant of human energy expenditure during non-stressed, eucaloric conditions
Effects of Short-Term Fasting on Ghrelin/GH/IGF-1 Axis in Healthy Humans: the Role of Ghrelin in the Thrifty Phenotype
No full textA greater decrease in 24-hour energy expenditure (24hEE) during short-term fasting is indicative of a thrifty phenotype. As ghrelin and the growth hormone (GH) - insulin-like growth factor 1 (IGF-1) axis are implicated in the regulation of energy intake and metabolism, we investigated whether ghrelin, GH and IGF-1 concentrations mediate the fasting-induced decrease in 24hEE that characterizes thriftiness
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