Insulin and central regulation of spontaneous fattening and weight loss

1985 ◽  
Vol 249 (2) ◽  
pp. R203-R208
Author(s):  
R. B. Melnyk ◽  
J. M. Martin

Insulin binding to receptors in a partially purified hypothalamic membrane preparation is altered by prolonged starvation. To define further the relationship between hypothalamic insulin binding and energy balance, we studied the Richardson's ground squirrel, a hibernator that exhibits spontaneous 6- to 8-mo body weight cycles when kept in constant conditions. Isolated pancreatic islets from squirrels killed during the weight gain phase had greater glucose-stimulated insulin secretion than those from weight loss phase animals, and adipocytes showed significantly greater glucose incorporation into total lipid in response to insulin. Differences in lipogenesis were not attributable to changes in insulin-binding capacity. Hypothalamic tissue from weight gain phase animals bound more insulin than that from weight loss phase animals. Maximal binding was correlated with pancreatic islet responsiveness and maximal insulin-stimulated lipogenesis. The strong positive correlation between peripheral metabolic events associated with spontaneous alterations in energy balance and the binding kinetics of hypothalamic insulin receptors suggests that insulin may play an important role in the central regulation of body weight.

2002 ◽  
Vol 9 (4) ◽  
pp. 771-776 ◽  
Author(s):  
Frédéric Picard ◽  
Denis Arsenijevic ◽  
Denis Richard ◽  
Yves Deshaies

ABSTRACT Infection of male Swiss Webster mice with Toxoplasma gondii or Neospora caninum leads to long-term alterations in energy balance. Following an initial 20 to 30% weight loss in all T. gondii-infected mice, half of the animals regain most of the lost weight (gainers), whereas the others maintain their low body weight (nongainers). Infection with N. caninum does not elicit weight loss. Lipoprotein lipase (LPL), the enzyme responsible for plasma triglyceride (TG) clearance and partitioning among tissues, is under tissue-specific modulation associated with energy balance. It is also a major determinant of infection-induced hypertriglyceridemia. This study aimed to assess the long-term modulation of adipose and muscle LPL activity in mice infected with T. gondii or N. caninum, to evaluate the effects of subsequent acute lipopolysaccharide (LPS) administration, and to relate LPL modulation in these conditions with infection-related changes in body weight gain. Twenty-eight days after infection, LPL activity in muscle of both gainer and nongainer T. gondii-infected mice was reduced by 40 to 50% compared with the levels in controls and N. caninum-infected mice, whereas LPL activity in adipose depots remained unchanged in all infected groups compared to the level in controls. LPS (from Escherichia coli, 100 ng/kg) injection induced a global reduction in adipose LPL in all groups, as assessed 90 min later. In both T. gondii-infected subgroups, muscle LPL was not further reduced by LPS treatment, whereas it was decreased by 40 to 50% in muscles of control and N. caninum-infected mice. Pre-LPS TG levels in plasma were similar in all groups. LPS greatly increased TG levels in plasma in both control and N. caninum-infected animals, whereas it did not alter those of T. gondii-infected gainer or nongainer animals. These results show that (i) independently of the extent of postinfection weight gain, long-term infection with T. gondii chronically reduces muscle LPL, which becomes unresponsive to acute endotoxemia; (ii) modulation of tissue LPL activity during chronic T. gondii infection favors TG partitioning towards adipose tissue; and (iii) skeletal muscle LPL is a key determinant of the acute response of triglyceridemia to LPS.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1359
Author(s):  
Noga C Minsky ◽  
Dafna Pachter ◽  
Galia Zacay ◽  
Naama Chishlevitz ◽  
Miriam Ben-Hamo ◽  
...  

Since the outbreak of COVID-19, billions of people have gone into lockdown, facing pandemic related challenges that engender weight gain, especially in the obese. We report the results of an online survey, conducted during Israel’s first quarantine, of 279 adults treated in hospital-based obesity clinics with counseling, medications, surgery, endoscopic procedures, or any combination of these for weight loss. In this study, we assessed the association between changes in dietary and lifestyle habits and body weight, and the benefits of receiving weight management care remotely through telemedicine during lockdown. Compared to patients not receiving obesity care via telemedicine, patients receiving this care were more likely to lose weight (OR, 2.79; p = 0.042) and also to increase participation in exercise (OR, 2.4; p = 0.022). While 40% of respondents reported consuming more sweet or salty processed snacks and 33% reported less vegetables and fruits, 65% reported more homemade foods. At the same time, 40% of respondents reported a reduction in exercise and 52% reported a decline in mood. Alterations in these eating patterns, as well as in exercise habits and mood, were significantly associated with weight changes. This study highlights that lockdown affects health behaviors associated with weight change, and advocates for the use of telemedicine to provide ongoing obesity care during future quarantines in order to promote weight loss and prevent weight gain.


2016 ◽  
Vol 48 (7) ◽  
pp. 491-501 ◽  
Author(s):  
Madeliene Stump ◽  
Deng-Fu Guo ◽  
Ko-Ting Lu ◽  
Masashi Mukohda ◽  
Xuebo Liu ◽  
...  

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Win Hlaing Than ◽  
Jack K C Ng ◽  
Gordon C K Chan ◽  
Winston Fung ◽  
Cheuk Chun Szeto

Abstract Background and Aims The prevalence of obesity has increased over the past decade in patients with End Stage Kidney Disease (ESKD). Obesity at the initiation of peritoneal dialysis (PD) was reported to adversely affect clinical outcomes. However, there are few studies on the prognostic relevance of weight gain after PD. Method We reviewed the change in body weight of 954 consecutive PD patients from the initiation of dialysis to 2 years after they remained on PD. Clinical outcomes including patient survival, technique survival, and peritonitis rate in the subsequent two years were reviewed. Results The mean age was 60.3 ± 12.2 years; 535 patients (56.1%) were men and 504 (52.8%) had diabetes. After the first 2 years on PD, the average change in body weight was 1.2± 5.1 kg; their body weight was 63.0 ± 13.3 kg; body mass index (BMI) 24.4 ± 4.4 kg/m2. The patient survival rates in the subsequent two years were 64.9%, 75.0%, and 78.9% (log rank test, p = 0.008) for patients with weight loss ≥3 kg during the first 2 years of PD weight change between -3 and +3 kg, and weight gain ≥3 kg, respectively. The corresponding technique survival rates in the subsequent two years were 93.1%, 90.1%, 91.3%, respectively (p = 0.110), and the peritonitis rates were 0.7±1.5, 0.6±1.7, and 0.6±1.1 episodes per patient-year, respectively (p = 0.3). When the actual BMI after the first 2 years of PD was categorized into underweight, normal weight, marginal overweight, overweight, and obesity groups, the patient survival rates in the subsequent two years were 77.3%, 75.2%, 73.3%, 74.3%, and 75.9%, respectively (p= 0.005), and technique survival 98.0%, 91.9%, 88.0%, 92.8%, and 81.0%, respectively (p= 0.001). After adjusting for confounding clinical factors by multivariate Cox regression models, weight gain ≥ 3kg during the first 2 years of PD was an independent protective factor for technique failure (adjusted hazard ratio [AHR] 0.049; 95% confidence interval [CI] 0.004-0.554, p = 0.015), but was an adverse predictor of patient survival (AHR 2.338, 95%CI 1.149-4.757, p = 0.019). In contrast, weight loss ≥ 3kg during the first 2 years of PD did not predict subsequent patient or technique survival. Conclusion Weight gain during the first 2 years of PD confers a significant risk of subsequent mortality but appears to be associated with a lower risk of technique failure. The mechanism of this discordant risk prediction deserves further study.


2000 ◽  
Vol 90 (2) ◽  
pp. 453-456 ◽  
Author(s):  
Thomas F. Cash ◽  
Melissa A. Brown

Antidepressant drugs are frequently prescribed for women and have various side effects, including potential effects on body weight. This experiment examined the effects of information about the weight-related side effects of antidepressants on women's attitudes toward the drugs. 60 college women were randomly assigned to read about one of two drugs, fluoxetine (Prozac) or Imipramine (Tofranil). Participants were either told or not told about veridical weight-related side effects, namely, weight loss for Prozac and weight gain for Tofranil. As hypothesized, weight-gain information lowered the personal acceptability of Tofranil, and weight-loss information enhanced the acceptability of Prozac. Although research with clinical populations is required, undergraduate women's decisions about the use of antidepressant medications may be influenced by societal body-image ideals.


1984 ◽  
Vol 107 (1) ◽  
pp. 86-90 ◽  
Author(s):  
Roman B. Melnyk ◽  
J. M. Martin

Abstract. We have previously shown that [125I]insulin binding to medial hypothalamic receptors is attenuated following 14 days of food restriction. Such rats are characterized by considerably reduced circulating insulin levels with unchanged hypothalamic insulin concentration. The present data demonstrate that, in contrast to the effects of starvation, [125I]insulin binding to hypothalamic receptors from rats made hyperinsulinaemic by daily injections of protamine zinc insulin (4–6 U/rat/day for 14 days) is unaffected by this manipulation, even though hypothalamic insulin concentration in insulininjected animals was significantly higher than in salineinjected controls. Insulin binding to partially purified membranes from the medial hypothalamic region was significantly greater than that from the lateral area, confirming a finding in our earlier study. Insulin treatment was associated with slight reductions in maximal insulin-binding capacity of medial hypothalamic receptors, a tendency which appeared to be compensated by reciprocal changes in receptor affinity for this hormone. The data indicate that hypothalamic insulin receptors are not regulated by peripheral or even central insulin levels per se; it appears, rather, that some other, as yet unidentified, correlate(s) of significantly altered food intake and/or body weight can modify hypothalamic insulin receptor function. Perhaps such modifications could, in turn, participate in the activation of regulatory mechanisms involved in correcting energy imbalance.


1989 ◽  
Vol 257 (3) ◽  
pp. R550-R555 ◽  
Author(s):  
S. Rivest ◽  
J. Landry ◽  
D. Richard

The purpose of the present study was to investigate both the respective and interactive roles of exercise training and testosterone on energy balance. Male rats were divided into sedentary and exercise-trained groups. Each group formed was further divided into a sham-operated group, an orchidectomized group, or an orchidectomized group treated with testosterone. Rats were exercised on a motor-driven treadmill for 1 h/day over 28 consecutive days, after which rats were killed. Energy balance measurements, body composition analyses, and serum testosterone assay were then performed. The weight, protein content, and cytochrome-c oxidase activity of interscapular brown adipose tissue (IBAT) were also measured. Results indicate that total food intake, final body weight, and body weight gain were generally lower in exercise-trained rats than in sedentary animals. In orchidectomized rats treated with testosterone, gains of both fat and protein were lower in exercise-trained than in sedentary animals. There was no difference in metabolizable energy intake and body energy gain between trained and sedentary rats that underwent orchidectomy without replacement therapy. In orchidectomized groups of rats, energy gain was lower in trained rats that were treated with testosterone than in those that did not receive any treatment. Furthermore, in trained orchidectomized rats treated with testosterone, both energetic efficiency and energy density of body weight gain were lower than those of trained orchidectomized rats that were not treated. Finally, a significant reduction in IBAT weight was observed in exercise-trained animals, whereas neither exercise nor the various hormonal manipulations affected IBAT protein content and cytochrome-c oxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)


2004 ◽  
Vol 91 (3) ◽  
pp. 479-484 ◽  
Author(s):  
Alejandro E. Macias

The existence of a set-point for homeostatic control of human body weight is uncertain. To investigate its existence, technically difficult determinations of energy expenditure must be performed: this has resulted in contradictory reports. The present study was performed with new methods in two stages (77 and 133d respectively). Two healthy male subjects with rigorously controlled physical activity ingested three standardized diets of processed foods from the same manufacturer. Hypo-, iso- and hyperenergetic diets containing 6255kJ (1494kcal), 10073kJ (2406kcal) and 13791kJ (3294kcal) respectively were ingested during alternate periods; changes in body weight were measured. A new index of energy expenditure was calculated as the amount of weight lost in an 8h overnight period (WL8H). A digital scale was used in stage 1 and a mechanical scale in stage 2. The change in body weight in response to the isoenergetic diet differed according to the circumstances. In basal conditions, it was associated with weight stability. After weight loss from energy restriction, the isoenergetic diet led to weight gain. After weight gain from overeating, it led to weight loss. Diets of higher energy content were associated with greater WL8H (F>20; P<0·0001 for both subjects). Measurement variability was lower using a mechanical scale. The present study demonstrates the existence of a homeostatic control of human weight and describes a new index of energy expenditure measured in weight units. It also demonstrates that strict dietary supervision for months is possible. Investigation of the human body weight set-point is vital in understanding obesity.


1984 ◽  
Vol 39 (1-2) ◽  
pp. 183-185 ◽  
Author(s):  
G. Csaba ◽  
P. Kovács ◽  
Ágnes Inczefi-Gonda

Abstract Tetrahvmena cells treated with purified rabbit anti­ bodies to rat hepatocellular membrane exhibited a consider­ able increase in binding capacity on reexposure to the antibody 24 h later. Insulin binding was similarly enhanced by preexposure to the antibody, and vice versa, preex­ posure to insulin enhanced the later binding of rat liver receptor antibodies. This suggests that (1) the Tetrahymena and the rat possess similar insulin receptors, and (2) the receptor antibody is also able to induce imprinting for itself as well as for insulin. Concanavalin-A, noted for binding overlap with insulin, failed to induce imprinting either for insulin or for antibodies to receptors, whereas the latter did induce imprinting for Concanavalin-A.


Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1371
Author(s):  
Kelly Giudici ◽  
Sophie Guyonnet ◽  
Yves Rolland ◽  
Bruno Vellas ◽  
Philipe de Souto Barreto ◽  
...  

This study aimed to analyze associations between weight variation patterns and changes in cognitive function and hippocampal volume among non-demented, community-dwelling elderly. Sample was formed of 1394 adults >70 years (63.9% female), all volunteers from the Multidomain Alzheimer Preventive Trial (MAPT). Weight loss was defined as ≥5% of body weight decrease in the first year of follow-up; weight gain as ≥5% of weight increase; and stability if <5% weight variation. Cognition was examined by a Z-score combining four tests. Measures were assessed at baseline, 6, 12, 24, 36, 48, and 60 months of follow-up. Hippocampal volume was evaluated with magnetic resonance imaging in 349 subjects in the first year and at 36 months. Mixed models were performed. From the 1394 participants, 5.5% (n = 76) presented weight loss, and 9.0% (n = 125) presented weight gain. Cognitive Z-score decreased among all groups after 5 years, but decline was more pronounced among those who presented weight loss (adjusted between-group mean difference vs. stable: −0.24, 95%CI: −0.41 to −0.07; p = 0.006). After 3 years, hippocampal atrophy was observed among all groups, but no between-group differences were found. In conclusion, weight loss ≥5% in the first year predicted higher cognitive decline over a 5 year follow-up among community-dwelling elderly, independently of body mass index.


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