Consuming sucrose solution promotes leptin resistance and site specifically modifies hypothalamic leptin signaling in rats

2020 ◽  
Author(s):  
Ruth B.S. Harris
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Sucrose Solution ◽  
Ventromedial Hypothalamus ◽  
Primary Response ◽  
Leptin Resistance ◽  
Sprague Dawley ◽  
Leptin Signaling ◽  
Transient Rise

Rats consuming 30% sucrose solution and a sucrose-free diet (LiqS) become leptin resistant whereas rats consuming sucrose from a formulated diet (HS) remain leptin responsive. This study tested whether leptin resistance in LiqS rats extended beyond a failure to inhibit food intake and examined leptin responsiveness in the hypothalamus and hindbrain of rats offered HS, LiqS or a sucrose free diet (NS). Female LiqS Sprague Dawley rats initially only partially compensated for the calories consumed as sucrose, but energy intake matched that of HS and NS rats when they were transferred to calorimetry cages. There was no effect of diet on energy expenditure, IBAT temperature or fat pad weight. A peripheral injection of 2 mg leptin/kg on Day 23 or 26 inhibited energy intake of HS and NS, but not LiqS rats. Inhibition occurred earlier in HS than NS rats and was associated with a smaller meal size. Leptin had no effect on energy expenditure, but caused a transient rise in IBAT temperature of HS rats. Leptin increased pSTAT3 in the hindbrain and ventromedial hypothalamus of all rats. There was a minimal effect of leptin in the arcuate nucleus and only the dorsomedial hypothalamus showed a correlation between pSTAT3 and leptin responsiveness. These data suggest that the primary response to leptin is inhibition of food intake and that the pattern of sucrose consumption, rather than calories consumed as sucrose causes leptin resistance associated with site specific differences in hypothalamic leptin signaling.

scholarly journals Selective Inactivation of Socs3 in SF1 Neurons Improves Glucose Homeostasis without Affecting Body Weight

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5654-5661 ◽  
Author(s):  
Ren Zhang ◽  
Harveen Dhillon ◽  
Huali Yin ◽  
Akihiko Yoshimura ◽  
Bradford B. Lowell ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
Leptin Resistance ◽  
High Fat ◽  
Leptin Signaling ◽  
Leptin Sensitivity ◽  
High Fat Diets ◽  
Fat Diets

Suppressor of cytokine signaling 3 (Socs3) has been identified as a mediator of central leptin resistance, but the identity of specific neurons in which Socs3 acts to suppress leptin signaling remains elusive. The ventromedial hypothalamus (VMH) was recently shown to be an important site for leptin action because deleting leptin receptor within VMH neurons causes obesity. To examine the role of VMH Socs3 in leptin resistance and energy homeostasis, we generated mice lacking Socs3 specifically in neurons positive for steroidogenic factor 1 (SF1), which is expressed abundantly in the VMH. These mice had increased phosphorylation of signal transducer and activator of transcription-3 in VMH neurons, suggesting improved leptin signaling, and consistently, food intake and weight-reducing effects of exogenous leptin were enhanced. Furthermore, on either chow or high-fat diets, these mice had reduced food intake. Unexpectedly, energy expenditure was reduced as well. Mice lacking Socs3 in SF1 neurons, despite no change in body weight, had improved glucose homeostasis and were partially protected from hyperglycemia and hyperinsulinemia induced by high-fat diets. These results suggest that Socs3 in SF1 neurons negatively regulates leptin signaling and plays important roles in mediating leptin sensitivity, glucose homeostasis, and energy expenditure.

scholarly journals Hyperphagia and Central Mechanisms for Leptin Resistance during Pregnancy

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1355-1365 ◽  
Author(s):  
M. L Trujillo ◽  
C. Spuch ◽  
E. Carro ◽  
R. Señarís
Keyword(s):  
Food Intake ◽  
Late Pregnancy ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
Sprague Dawley ◽  
Leptin Signaling ◽  
Akt Phosphorylation ◽  
Pomc Mrna ◽  
Intake Regulation ◽  
Maternal Hormones

Abstract The purpose of this work was to study the central mechanisms involved in food intake regulation and leptin resistance during gestation in the rat. Sprague Dawley rats of 7, 13, and 18 d of pregnancy [days of gestation (G) 7, G13, and G18] were used and compared with nonpregnant animals in diestrus-1. Food intake was already increased in G7, before hyperleptinemia and central leptin resistance was established in midpregnancy. Leptin resistance was due to a reduction in leptin transport through the blood-brain barrier (BBB) and to alterations in leptin signaling within the hypothalamus based on an increase in suppressor of cytokine signaling 3 levels and a blockade of signal transducer and activator of transcription-3 phosphorylation (G13), followed by a decrease in LepRb and of Akt phosphorylation (G18). In early gestation (G7), no change in hypothalamic neuropeptide Y (NPY), agouti-related peptide (AgRP), or proopiomelanocortin (POMC) expression was shown. Nevertheless, an increase in NPY and AgRP and a decrease in POMC mRNA were observed in G13 and G18 rats, probably reflecting the leptin resistance. To investigate the effect of maternal vs. placental hormones on these mechanisms, we used a model of pseudogestation. Rats of 9 d of pseudogestation were hyperphagic, showing an increase in body and adipose tissue weight, normoleptinemia, and normal responses to iv/intracerebroventricular leptin on hypothalamic leptin signaling, food intake, and body weight. Leptin transport through the BBB, and hypothalamic NPY, AgRP and POMC expression were unchanged. Finally, the transport of leptin through the BBB was assessed using a double-chamber culture system of choroid plexus epithelial cells or brain microvascular endothelial cells. We found that sustained high levels of prolactin significantly reduced leptin translocation through the barrier, whereas progesterone and β-estradiol did not show any effect. Our data demonstrate a dual mechanism of leptin resistance during mid/late-pregnancy, which is not due to maternal hormones and which allows the maintenance of hyperphagia in the presence of hyperleptinemia driven by an increase in NPY and AgRP and a decrease in POMC mRNA. By contrast, in early pregnancy maternal hormones induce hyperphagia without the regulation of hypothalamic NPY, AgRP, or POMC and in the absence of leptin resistance.

scholarly journals Severe protein deficiency induces hepatic expression and systemic level of FGF21 but inhibits its hypothalamic expression in growing rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joanna Moro ◽  
Catherine Chaumontet ◽  
Patrick C. Even ◽  
Anne Blais ◽  
Julien Piedcoq ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Dietary Protein ◽  
Protein Deficiency ◽  
Protein Diet ◽  
Growing Rats ◽  
Low Protein ◽  
Protein Diets

AbstractTo study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.

scholarly journals Region-Specific Reduction in Leptin-Induced Phosphorylation of Signal Transducer and Activator of Transcription-3 (STAT3) in the Rat Hypothalamus Is Associated with Leptin Resistance during Pregnancy

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3704-3711 ◽  
Author(s):  
S. R. Ladyman ◽  
D. R. Grattan
Keyword(s):  
Food Intake ◽  
Arcuate Nucleus ◽  
Ventromedial Hypothalamus ◽  
Leptin Resistance ◽  
Signal Transducer ◽  
Pregnant Rats ◽  
Hypothalamic Nuclei ◽  
Stat3 Phosphorylation ◽  
Vehicle Treatment ◽  
Plasma Leptin

Abstract Leptin concentrations increase during pregnancy, but this does not prevent the pregnancy-induced increase in food intake, suggesting a state of leptin resistance. This study investigated the response to intracerebroventricular leptin administration in pregnant rats. After fasting, nonpregnant, d-7 and d-14 pregnant rats received leptin (4 μg) or vehicle, then food intake was measured. Serial blood samples were collected in another group of rats to determine plasma leptin concentrations. Further groups of d-14 pregnant and nonpregnant rats were killed after leptin or vehicle treatment, and brains were collected. Hypothalamic nuclei were microdissected, and levels of signal transducer and activator of transcription (STAT)3 phosphorylation were measured using Western blot analysis. Fasting decreased leptin concentrations in both pregnant and nonpregnant rats. Leptin treatment significantly reduced food intake in nonpregnant and d-7 pregnant rats but not in d-14 pregnant rats. In addition, there was no postfasting hyperphagic response in the pregnant rats. In the pregnant rats, leptin-induced STAT3 phosphorylation was suppressed in the arcuate nucleus and, to a lesser extent, in the ventromedial hypothalamus (VMH), compared with nonpregnant rats. Unstimulated STAT3 levels were also decreased in the VMH during pregnancy. Leptin-induced phosphorylation of STAT3 in the dorsomedial and lateral hypothalamus was not different between pregnant and nonpregnant rats. These data indicate that pregnant rats become resistant to the satiety action of leptin. Furthermore, leptin-induced activation of the STAT3 is impaired during pregnancy, specifically in the arcuate nucleus and VMH. These data support the hypothesis that pregnancy is a state of hypothalamic leptin resistance.

Nutrition: Macronutrient metabolism

2020 ◽  
pp. 1839-1854
Author(s):  
Keith N. Frayn ◽  
Rhys D. Evans
Keyword(s):  
Amino Acids ◽  
Food Intake ◽  
Energy Expenditure ◽  
Complex Systems ◽  
Metabolic Control ◽  
Energy Intake ◽  
Energy Supply ◽  
The Body ◽  
Daily Lives ◽  
Storage Pools

Food intake is sporadic and, in many cultures, occurs in three daily boluses. At the same time, energy expenditure is continuous and can vary to a large extent independently of the pattern of energy intake, although fixed or predictable demands (e.g. through occupation) means that in most persons food intake and energy expenditure are soon balanced. The body has developed complex systems that direct excess nutrients into storage pools; as they are needed, they also regulate the mobilization of nutrients from these pools. Carbohydrate, lipid, and protein (the latter a source of amino acids) are the three types of energy supply that are stored variably and assimilated from food each day. That we can carry on our daily lives without thinking about whether to store or mobilize fuels, and which to use, attests to the remarkable efficiency and refinement of these systems of metabolic control.

Regulatory alterations of daily energy expenditure induced by fasting or overfeeding in unrestrained rats

1987 ◽  
Vol 63 (2) ◽  
pp. 465-470 ◽  
Author(s):  
H. Shibata ◽  
L. J. Bukowiecki
Keyword(s):  
Energy Expenditure ◽  
Energy Intake ◽  
Normal Values ◽  
Sucrose Solution ◽  
Normal Diet ◽  
The Other ◽  
O2 Consumption ◽  
Daily Energy Expenditure ◽  
Daily Energy ◽  
Ad Libitum

The consequences of fasting or overfeeding during 2 days on energy expenditure were investigated by continuously monitoring O2 consumption in unrestrained, unanesthetized rats. O2 consumption decreased by 15% on the 1st day of fasting and then by an additional 15% on the 2nd day. On the 3rd day, when rats were fed again, energy intake increased by 30% above control (prefasting) values, whereas energy expenditure rapidly increased but no more than control values. On the other hand, when ad libitum fed animals were offered a sucrose solution (32%) for 2 days, energy intake increased by 30% and energy expenditure by 9–12%. On the 3rd day, when the rats were fed with their normal diet, energy intake significantly decreased under control (preoverfeeding) values during one day, but energy expenditure rapidly returned to normal values. The results show that fasting decreases, whereas hyperphagia increases 24-h energy expenditure during the treatments. When the treatments are terminated, energy expenditure rapidly returns to normal values, but fasting induces a postfasting increase of energy intake (during 2 days), whereas hyperphagia, on the contrary, results in a transient decrease of appetite. This indicates that alterations of food intake induce compensatory changes of energy expenditure during the treatments, but that after the treatments, energy balance is normalized via regulatory adjustments in the ratio of energy expenditure over energy intake.

scholarly journals What processes are involved in the appetite response to moderate increases in exercise-induced energy expenditure?

1999 ◽  
Vol 58 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Neil A. King
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Weak Coupling ◽  
Eating Behaviour ◽  
Tight Coupling ◽  
Living Situation ◽  
Energy Value ◽  
Exercise Induced ◽  
Response To Exercise

It is intuitive that an energy deficit induced by exercise induces an automatic increased drive for food (hunger and energy intake). However, the absence of a compensatory increase in energy intake (EI) in response to an exercise-induced increase in energy expenditure (EE) is now well documented. Thus, there is a weak coupling between exercise-induced increases in EE and EI. One paradox related to the phenomenon of a weak coupling between the exercise-induced EE and EI is the observation of a positive relationship between physical activity and food intake in the long-term free-living situation (i.e. tight coupling between EE and EI). It is possible, therefore, that a period of transition (uncoupling) occurs in the short-term, before a steady-state (coupling) condition is achieved. It is likely that a combination of physiological and behavioural adaptations occur in order to achieve a tight coupling between EE and EI. The precise physiological and behavioural changes that take place to obtain a new equilibrium (i.e. coupling between EE and EI) are still undetermined. The expectation that exercise-induced increases in EE should drive up hunger and food intake tends to be based on the concept of a strong coupling between physiology and behaviour. However, because of the individual's strong volitional control over eating behaviour, the psychological influences on the appetite response to exercise should not be undervalued. The psychological position of the individual (e.g. dietary restraint, food-related cognitions, reasons for exercising) could have a very strong influence on the food intake response to exercise. Misjudgements concerning the energy value of the food (EI) relative to the energy value of the exercise (EE) could be one possibility why exercise fails to be a successful method of weight loss for some individuals.

scholarly journals Validation of the Danish 7-day pre-coded food diary among adults: energy intake v. energy expenditure and recording length

2009 ◽  
Vol 102 (12) ◽  
pp. 1838-1846 ◽  
Author(s):  
Anja Biltoft-Jensen ◽  
Jeppe Matthiessen ◽  
Lone B. Rasmussen ◽  
Sisse Fagt ◽  
Margit V. Groth ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Group Level ◽  
Food Diary ◽  
Dietary Survey ◽  
Limits Of Agreement ◽  
Free Living ◽  
Food Items ◽  
In The Beginning

Under-reporting of energy intake (EI) is a well-known problem when measuring dietary intake in free-living populations. The present study aimed at quantifying misreporting by comparing EI estimated from the Danish pre-coded food diary against energy expenditure (EE) measured with a validated position-and-motion instrument (ActiReg®). Further, the influence of recording length on EI:BMR, percentage consumers, the number of meal occasions and recorded food items per meal was examined. A total of 138 Danish volunteers aged 20–59 years wore the ActiReg® and recorded their food intake for 7 consecutive days. Data for 2504 participants from the National Dietary Survey 2000–2 were used for comparison of characteristics and recording length. The results showed that EI was underestimated by 12 % on average compared with EE measured by ActiReg® (PreMed AS, Oslo, Norway). The 95 % limits of agreement for EI and EE were − 6·29 and 3·09 MJ/d. Of the participants, 73 % were classified as acceptable reporters, 26 % as under-reporters and 1 % as over-reporters. EI:BMR was significantly lower on 1–3 consecutive recording days compared with 4–7 recording days (P < 0·03). Percentage consumers of selected food items increased with number of recording days. When recording length was 7 d, the number of reported food items per meal differed between acceptable reporters and under-reporters. EI:BMR was the same on 4 and 7 consecutive recording days. This was, however, a result of under-reporting in the beginning and the end of the 7 d reporting. Together, the results indicate that EI was underestimated at group level and that a 7 d recording is preferable to a 4 d recording period.

scholarly journals Increased Hypothalamic Protein Tyrosine Phosphatase 1B Contributes to Leptin Resistance with Age

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 433-440 ◽  
Author(s):  
Christopher D. Morrison ◽  
Christy L. White ◽  
Zhong Wang ◽  
Seung-Yub Lee ◽  
David S. Lawrence ◽  
...  
Keyword(s):  
Food Intake ◽  
Protein Tyrosine Phosphatase ◽  
Middle Age ◽  
Tyrosine Phosphatase ◽  
Leptin Resistance ◽  
Protein Tyrosine Phosphatase 1B ◽  
Sprague Dawley ◽  
Protein Tyrosine ◽  
Leptin Sensitivity ◽  
Old Rats

Animals at advanced ages exhibit a reduction in central leptin sensitivity. However, changes in growth, metabolism, and obesity risk occur much earlier in life, particularly during the transition from youth to middle age. To determine when initial decreases in central leptin sensitivity occur, leptin-dependent suppression of food intake was tested in 8-, 12-, and 20-wk-old male, chow-fed Sprague Dawley rats. Intracerebroventricular leptin injection (3 μg) suppressed 24-h food intake in 8- and 12-wk-old rats (P &lt; 0.05) but not 20-wk-old rats. To identify potential cellular mediators of this resistance, we focused on protein tyrosine phosphatase 1B (PTP1B), a recently described inhibitor of leptin signaling. PTP1B protein levels, as determined by Western blot, were significantly higher in mediobasal hypothalamic punches collected from 20-wk-old rats, compared with 8-wk-old rats (P &lt; 0.05). When 20-wk-old rats were fasted for 24 h, levels of hypothalamic PTP1B decreased (P &lt; 0.05), coincident with a restoration of leptin sensitivity. To directly test whether inhibition of PTP1B restores leptin sensitivity, 20-wk-old chow-fed rats were pretreated with a pharmacological PTP1B inhibitor 1 h before leptin, and 24-h food intake was recorded. As expected, leptin alone produced a small but nonsignificant reduction in food intake. However, pretreatment with the PTP1B inhibitor resulted in a marked improvement in leptin-dependent suppression of food intake (P &lt; 0.05). These data are consistent with the hypothesis that increases in PTP1B contribute to hypothalamic leptin resistance as rats transition into middle age.

scholarly journals Cold-induced hyperphagia requires AgRP-neuron activation in mice

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jennifer Deem ◽  
Chelsea L Faber ◽  
Christian Pedersen ◽  
Bao Anh Phan ◽  
Sarah A Larsen ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Cold Exposure ◽  
Energy Homeostasis ◽  
Cold Environment ◽  
Energy Demands ◽  
Acute Cold Exposure ◽  
Neuron Activation ◽  
Increase Food Intake

To maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP-neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake but has no effect on energy expenditure. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure.

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