Circulating ghrelin in thyroid dysfunction is related to insulin resistance and not to hunger, food intake or anthropometric changes

Objective: Ghrelin is a gastric peptide that plays a role in appetite stimulation, energy balance and possibly in insulin resistance. Hyperthyroidism is a situation where negative energy balance and insulin resistance coexist, while in hypothyroidism a positive energy balance and normal insulin sensitivity predominate. We investigated ghrelin levels and their relationship with hunger, food intake and both anthropometric and insulin resistance parameters in patients with thyroid dysfunction. Design and methods:We studied 24 hyperthyroid and 17 hypothyroid patients before and after normalisation of thyroid hormone levels and their respective body mass index (BMI)-matched control group. We measured plasma ghrelin levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, a hunger score, mean three-day calorie intake and anthropometric parameters. Results: In hyperthyroidism, HOMA-IR index was higher (3.21 ± 0.60 vs 1.67 ± 0.15mMmU/l; P = 0.014, t test for independent data) and ghrelin levels were lower (463.6 ± 36.4 vs 561.1 ± 32.1 pg/ml; P = 0.041, Mann–Whitney U-test) than in its control group and both normalised after treatment (HOMA-IR: 2.28 ± 0.38mMmU/l; P = 0.106, t test for independent data, and ghrelin: 539.7 ± 45.4 pg/ml; P = 0.549, Mann–Whitney U-test). Glucose, as a component of HOMA-IR index was the only predictor for ghrelin levels (β = −0.415, P = 0.044, stepwise multiple regression analysis). In hypothyroidism, HOMA-IR index and ghrelin levels were similar to those in its control group both before and after treatment. In both thyroid dysfunction states, no correlations were observed between changes in ghrelin levels and in free T4, free T3, anthropometric parameters, total calorie intake and hunger score. Conclusions: In thyroid dysfunction states, ghrelin levels seemed to be in relation to insulin resistance and not to energy balance and food intake regulation, as seen in other physiological and pathological states.

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Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity

Scientific Reports ◽

10.1038/s41598-021-96278-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Irene Cimino ◽

Debra Rimmington ◽

Y. C. Loraine Tung ◽

Katherine Lawler ◽

Pierre Larraufie ◽

...

Keyword(s):

Body Weight ◽

Energy Balance ◽

Food Intake ◽

Energy Expenditure ◽

Positive Energy ◽

Chow Diet ◽

Chromatin Regulator ◽

Positive Energy Balance ◽

The Impact ◽

Deficient Mice

AbstractNeuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat+/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat+/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat+/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat+/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat+/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat+/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.

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Session 2: Calorie-Cutting Keys

Effective Weight Loss ◽

10.1093/med:psych/9780190232009.003.0002 ◽

2016 ◽

pp. 15-26

Author(s):

Evan M. Forman ◽

Meghan L. Butryn

Keyword(s):

Energy Balance ◽

Food Intake ◽

Eating Behavior ◽

Negative Energy ◽

Negative Energy Balance ◽

Calorie Intake ◽

Self Monitoring ◽

Serving Size ◽

High Calorie

This chapter (Session 2) discusses the importance of self-monitoring to gain awareness of calorie intake and to recognize patterns in eating behavior. Clients are provided with information on how to self-monitor food intake, including recording type of food, serving size, method of preparation, and time of eating. Strategies for beginning to reduce calories are discussed, such as limiting high-calorie foods in the environment, eating regular meals, and planning meals in advance. The idea of achieving a negative energy balance is introduced, meaning that in order to lose weight, clients must expend a greater amount of energy than they consume in the form of calories.

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Hyperthyroidism-Associated Insulin Resistance Is Not Mediated by Adiponectin Levels

Journal of Thyroid Research ◽

10.4061/2011/194721 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Chih-Hsun Chu ◽

Hing-Chung Lam ◽

Jenn-Kuen Lee ◽

Chih-Chen Lu ◽

Chun-Chin Sun ◽

...

Keyword(s):

Insulin Resistance ◽

Plasma Concentrations ◽

Serum Glucose ◽

Antithyroid Drugs ◽

Control Group ◽

Model Assessment ◽

Insulin Levels ◽

Significant Difference ◽

Before And After ◽

Antithyroid Treatment

To evaluate the relationship between circulating adiponectin and insulin sensitivity in patients with hyperthyroid Graves' disease, we studied 19 adult patients with this disease and 19 age- and sex-matched euthyroid controls. All hyperthyroid patients were treated with antithyroid drugs and were re-evaluated after thyroid function normalized. Before antithyroid treatment, the adiponectin plasma concentrations were not different comparing with those in control group. The adiponectin levels remained unchanged after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) in hyperthyroid group was higher before treatment than after treatment. There was no significant difference in serum glucose and insulin levels between hyperthyroid and control groups and in the hyperthyroid group before and after treatment. BMI-adjusted adiponectin levels were not different among three groups. On the other hand, BMI-adjusted insulin levels and HOMA-IR values were significantly decreased after management of hyperthyroidism. Pearson's correlation revealed that insulin and HOMA-IR values positively correlated with triiodothyronine (T3) and free thyroxine (FT4) levels. However, adiponectin did not correlate with T3, FT4, insulin, HOMA-IR and thyrotropin receptor autoantibody (TRAb) levels. In conclusion, insulin resistance associated with hyperthyroidism is not mediated by the levels of plasma adiponectin.

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Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00040.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. E78-E84 ◽

Cited By ~ 45

Author(s):

Sabine Strassburg ◽

Stefan D. Anker ◽

Tamara R. Castaneda ◽

Lukas Burget ◽

Diego Perez-Tilve ◽

...

Keyword(s):

Body Weight ◽

Energy Balance ◽

Food Intake ◽

Energy Expenditure ◽

Therapeutic Potential ◽

Body Weight Gain ◽

Metabolic Effects ◽

Positive Energy ◽

High Dose ◽

Growth Hormone Secretagogue

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is the only circulating agent to powerfully promote a positive energy balance. Such action is mediated predominantly by central nervous system pathways controlling food intake, energy expenditure, and nutrient partitioning. The ghrelin pathway may therefore offer therapeutic potential for the treatment of catabolic states. However, the potency of the endogenous hormone ghrelin is limited due to a short half-life and the fragility of its bioactivity ensuring acylation at serine 3. Therefore, we tested the metabolic effects of two recently generated GHS-R agonists, BIM-28125 and BIM-28131, compared with ghrelin. All agents were administered continuously for 1 mo in doses of 50 and 500 nmol·kg−1·day−1 using implanted subcutaneous minipumps in rats. High-dose treatment with single agonists or ghrelin increased body weight gain by promoting fat mass, whereas BIM-28131 was the only one also increasing lean mass significantly. Food intake increased during treatment with BIM-28131 or ghrelin, whereas no effects on energy expenditure were detected. With the lower dose, only BIM-28131 had a significant effect on body weight. This also held true when the compound was administered by subcutaneous injection three times/day. No symptoms or signs of undesired effects were observed in any of the studies or treated groups. These results characterize BIM-28131 as a promising GHS-R agonist with an attractive action profile for the treatment of catabolic disease states such as cachexia.

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Regulation of serum leptin and its role in the hyperphagia of lactation in the rat

Journal of Endocrinology ◽

10.1677/joe.0.1760193 ◽

2003 ◽

Vol 176 (2) ◽

pp. 193-203 ◽

Cited By ~ 35

Author(s):

RG Denis ◽

G Williams ◽

RG Vernon

Keyword(s):

Energy Balance ◽

Food Intake ◽

Milk Production ◽

Litter Size ◽

High Energy ◽

Negative Energy ◽

Negative Energy Balance ◽

Calorie Intake ◽

Serum Leptin ◽

Nocturnal Rise

The factors regulating serum leptin concentration and its relationship to the hyperphagia of lactation have been investigated in rats. Lactation results in hypoleptinaemia and loss, or at least marked attenuation, of the nocturnal rise in serum leptin. Litter removal resulted in a fall in food intake and restoration of the nocturnal rise in serum leptin. Returning the litter to the mother after a 48-h absence increased food intake and began to reinitiate milk production, but the nocturnal serum leptin levels were still increased at 48 h after litter restoration. Adjusting litter size to four, eight, ten or fourteen pups at parturition resulted in different rates of litter growth and food intake during the subsequent lactation, but had no effect on the degree of hypoleptinaemia. Reducing litter size from ten to four pups at mid-lactation resulted in a transient increase in both serum leptin and pup growth rate, while food intake fell to a level found in rats suckling four pups throughout lactation. Reducing milk production by injection of bromocriptine increased serum leptin, but did not restore the nocturnal rise in serum leptin; food intake decreased, but remained much higher than in non-lactating rats. Feeding a varied, high-energy diet resulted in a decrease in the weight of food ingested, but no change in calorie intake, and had no effect on the hypoleptinaemia. These studies suggested that the hypoleptinaemia of lactating rats is due to negative energy balance, but the loss of the nocturnal rise in serum leptin is due to the suckling stimulus. The negative energy balance of lactation does not appear to be caused by a physical constraint on food intake. While the hypoleptinaemia should facilitate the hyperphagia of lactation, other orexigenic signals must also be involved.

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Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00632.2002 ◽

2003 ◽

Vol 284 (6) ◽

pp. R1399-R1408 ◽

Cited By ~ 34

Author(s):

Michael A. Statnick ◽

Frank C. Tinsley ◽

Brian J. Eastwood ◽

Todd M. Suter ◽

Charles H. Mitch ◽

...

Keyword(s):

Body Composition ◽

Energy Balance ◽

Food Intake ◽

Energy Intake ◽

Opioid Receptors ◽

Oral Treatment ◽

Positive Energy ◽

Reduce Food Intake ◽

Tissue Mass ◽

Obese Rats

Agonists to opioid receptors induce a positive energy balance, whereas antagonists at these receptors reduce food intake and body weight in rodent models of obesity. An analog of 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine, LY255582, is a potent non-morphinan antagonist for μ-, κ-, and δ-receptors ( K i of 0.4, 2.0, and 5.2 nM, respectively). In the present study, we examined the effects of oral LY255582 treatment on caloric intake, calorie expenditure, and body composition in dietary-induced obese rats. Acute oral treatment of LY255582 produced a dose-dependent decrease in energy intake and respiratory quotient (RQ), which correlated with the occupancy of central opioid receptors. Animals receiving chronic oral treatment with LY255582 for 14 days maintained a negative energy balance that was sustained by increased lipid use. Analysis of body composition revealed a reduction in fat mass accretion, with no change in lean body mass, in animals treated with LY255582. Therefore, chronic treatment with LY255582 reduces adipose tissue mass by reducing energy intake and stimulating lipid use.

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Meta-fibrosis links positive energy balance and mitochondrial metabolism to insulin resistance

F1000Research ◽

10.12688/f1000research.11653.1 ◽

2017 ◽

Vol 6 ◽

pp. 1758 ◽

Cited By ~ 4

Author(s):

Daniel S. Lark ◽

David H. Wasserman

Keyword(s):

Insulin Resistance ◽

Extracellular Matrix ◽

Energy Balance ◽

Positive Energy ◽

Extracellular Matrix Remodeling ◽

Low Grade ◽

Matrix Remodeling ◽

Matrix Expansion ◽

Positive Energy Balance ◽

Low Grade Inflammation

Obesity and insulin resistance often emerge from positive energy balance and generally are linked to low-grade inflammation. This low-grade inflammation has been called “meta-inflammation” because it is a consequence of the metabolic dysregulation that can accompany overnutrition. One means by which meta-inflammation is linked to insulin resistance is extracellular matrix expansion secondary to meta-inflammation, which we define here as “meta-fibrosis”. The significance of meta-fibrosis is that it reflects a situation in which the extracellular matrix functions as a multi-level integrator of local (for example, mitochondrial reactive oxygen species production) and systemic (for example, inflammation) inputs that couple to cellular processes creating insulin resistance. While adipose tissue extracellular matrix remodeling has received considerable attention, it is becoming increasingly apparent that liver and skeletal muscle extracellular matrix remodeling also contributes to insulin resistance. In this review, we address recent advances in our understanding of energy balance, mitochondrial energetics, meta-inflammation, and meta-fibrosis in the development of insulin resistance.

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Protective role of melatonin against adipose-hepatic metabolic comorbidities in experimentally induced obese rat model

PLoS ONE ◽

10.1371/journal.pone.0260546 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0260546

Author(s):

Mary J. Obayemi ◽

Christopher O. Akintayo ◽

Adesola A. Oniyide ◽

Ayodeji Aturamu ◽

Olabimpe C. Badejogbin ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Food Intake ◽

High Fat Diet ◽

Wistar Rats ◽

Liver Lipid ◽

Control Group ◽

Metabolic Dysfunction ◽

High Fat ◽

Male Wistar Rats

Background Adipose and hepatic metabolic dysfunctions are critical comorbidities that also aggravate insulin resistance in obese individuals. Melatonin is a low-cost agent and previous studies suggest that its use may promote metabolic health. However, its effects on some comorbidities associated with obesity are unknown. Herein, we investigated the hypothesis that melatonin supplementation would attenuate adipose-hepatic metabolic dysfunction in high fat diet (HFD)-induced obesity in male Wistar rats. Materials and methods Twenty-four adult male Wistar rats (n = 6/group) were used: Control group received vehicle (normal saline), obese group received 40% high fat diet, melatonin-treated group received 4 mg/kg of melatonin, and obese plus melatonin group received 40% HFD and melatonin. The treatment lasted for 12 weeks. Results HFD caused increased food intake, body weight, insulin level, insulin resistance and plasma and liver lipid but decreased adipose lipid. In addition, HFD also increased plasma, adipose and liver malondialdehyde, IL-6, uric acid and decreased Glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and circulating obestatin concentration. However, these deleterious effects except food intake were attenuated when supplemented with melatonin. Conclusion Taken together, the present results indicate that HFD exposure causes adipose-hepatic metabolic disturbance in obese animals, which are accompanied by oxidative stress and inflammation. In addition, the present results suggest that melatonin supplementation attenuates adipose-hepatic metabolic dysfunction, accompanying obesity by suppression of oxidative stress/inflammation-dependent mechanism and increasing circulating obestatin.

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Markers of inflammation and insulin resistance in dogs before and after weight loss versus lean healthy dogs

Pesquisa Veterinária Brasileira ◽

10.1590/1678-5150-pvb-6245 ◽

2020 ◽

Vol 40 (4) ◽

pp. 300-305

Author(s):

Juliana T. Jeremias ◽

Thiago H.A. Vendramini ◽

Roberta B.A. Rodrigues ◽

Mariana P. Perini ◽

Vivian Pedrinelli ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Body Fat ◽

Peptide Yy ◽

Body Condition Score ◽

Weight Loss Program ◽

Control Group ◽

Low Grade ◽

Markers Of Inflammation ◽

Before And After

ABSTRACT: Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory cytokines that contribute to insulin resistance. For this study body composition, markers of inflammation and of insulin resistance in dogs before and after weight loss were compared to those of lean dogs. Eleven client-owned obese adult dogs underwent a weight loss program with commercial dry food for weight loss and reached an ideal body condition score (BCS) six months after the beginning of the weight loss program. A Control Group of nine dogs with ideal BCS were selected for the comparison. Shapiro-Wilk test was used to test for normality, Mann Whitney were used for non-normally distributes data, and Student t-test was used for normally distributed parameters. In the Obese Group body fat decreased from 41.6% (30.7-58.6) to 29.1% (18.6-46.3) (P<0.01) and dogs maintained lean body mass throughout the weight loss program (P>0.05). Obese dogs presented higher concentration of fructosamine, triglycerides, insulin, IGF-1 and leptin than the Control Group before weight reduction (P<0.05). Serum concentrations of triglycerides, IL-2, IL-6, TNF-α, insulin, leptin and IGF-1 decreased after weight loss (P<0.01), and these concentrations were similar to the Control Group (P>0.05), except for leptin (P<0.001). No alteration on peptide YY was found. Leptin (r=0.60, P=0.01), fructosamine (r=0.44, P=0.02) and triglycerides (r=0.40, P=0.04) concentrations correlated with the reduction of body fat. Weight loss reduced the concentrations of inflammatory and insulin resistance markers and most parameters became similar to dogs that have always been lean, reinforcing the importance of weight loss in small animal practice.

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Effects of ad libitum food intake, insufficient sleep and weekend recovery sleep on energy balance

SLEEP ◽

10.1093/sleep/zsab136 ◽

2021 ◽

Author(s):

Christopher M Depner ◽

Edward L Melanson ◽

Robert H Eckel ◽

Janine A Higgins ◽

Bryan C Bergman ◽

...

Keyword(s):

Weight Gain ◽

Energy Balance ◽

Controlled Trial ◽

Sleep Restriction ◽

Positive Energy ◽

Control Group ◽

Weight Changes ◽

Insufficient Sleep ◽

Recovery Sleep ◽

Ad Libitum

Abstract Study Objectives Insufficient sleep is believed to promote positive energy balance (EB) and weight-gain. Increasing weekend sleep duration to “recover” from weekday sleep loss is common, yet little is known regarding how weekend recovery sleep influences EB. We conducted a randomized controlled trial to assess how: 1) 2 days and 8 days of insufficient sleep and 2) ad libitum weekend recovery sleep impact EB (energy intake [EI] – energy expenditure [EE]). Methods Following ten baseline days with 9h per night sleep opportunities, participants completed one of three 10-day experimental protocols with ad libitum EI: control (9h sleep opportunities; n=8; 23±5y [mean±SD]); sleep restriction (SR; 5h sleep opportunities; n=14; 25±5y); sleep restriction with weekend recovery sleep (SR+WR; 5 days insufficient sleep, 2 days ad libitum weekend recovery sleep, 3 days recurrent insufficient sleep; n=14; 27±4y). Results 24h EB increased (P < 0.001; main effect) by an average of 797.7±96.7 (±SEM) kcal during the 10-day experimental protocol versus baseline with no significant differences between groups. Percent change from baseline in 24h-EE was higher (P < 0.05) on day 2 of insufficient sleep (SR and SR+WR groups; 10±1%) versus adequate sleep (control group; 4±3%). Conclusions In this between-group study, the effects of adequate sleep and insufficient sleep, with or without or weekend recovery sleep, on 24h-EB were similar. Examining EB and body weight changes using within-subject cross-over designs and “free-living” conditions outside the laboratory (e.g., sleep extension) are needed to advance our understanding of the links between insufficient sleep, weekend recovery sleep and weight-gain.

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