scholarly journals Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats

2015 ◽  
Vol 308 (10) ◽  
pp. R872-R878 ◽  
Author(s):  
Christelle Le Foll ◽  
Ambrose A. Dunn-Meynell ◽  
Henry M. Miziorko ◽  
Barry E. Levin
Keyword(s):  
Food Intake ◽  
Potential Role ◽  
Ketone Bodies ◽  
Caloric Intake ◽  
High Energy ◽  
Leptin Resistance ◽  
Hypothalamic Nucleus ◽  
Diet Intake ◽  
Body Production

The objective of this study was to determine the potential role of astrocyte-derived ketone bodies in regulating the early changes in caloric intake of diet induced-obese (DIO) versus diet-resistant (DR) rats fed a 31.5% fat high-energy (HE) diet. After 3 days on chow or HE diet, DR and DIO rats were assessed for their ventromedial hypothalamic (VMH) ketone bodies levels and neuronal ventromedial hypothalamic nucleus (VMN) sensing using microdialysis coupled to continuous food intake monitoring and calcium imaging in dissociated neurons, respectively. DIO rats ate more than DR rats over 3 days of HE diet intake. On day 3 of HE diet intake, DR rats reduced their caloric intake while DIO rats remained hyperphagic. Local VMH astrocyte ketone bodies production was similar between DR and DIO rats during the first 6 h after dark onset feeding but inhibiting VMH ketone body production in DR rats on day 3 transiently returned their intake of HE diet to the level of DIO rats consuming HE diet. In addition, dissociated VMN neurons from DIO and DR rats were equally sensitive to the largely excitatory effects of β-hydroxybutyrate. Thus while DR rats respond to increased VMH ketone levels by decreasing their intake after 3 days of HE diet, this is not the case of DIO rats. These data suggest that DIO inherent leptin resistance prevents ketone bodies inhibitory action on food intake.

scholarly journals Fatty acid-induced astrocyte ketone production and the control of food intake

2016 ◽  
Vol 310 (11) ◽  
pp. R1186-R1192 ◽  
Author(s):  
Christelle Le Foll ◽  
Barry E. Levin
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Critical Role ◽  
Caloric Intake ◽  
Ventromedial Hypothalamus ◽  
Leptin Resistance ◽  
Metabolic Sensing ◽  
Total Fat ◽  
Metabolic Unit

Obesity and Type 2 diabetes are major worldwide public health issues today. A relationship between total fat intake and obesity has been found. In addition, the mechanisms of long-term and excessive high-fat diet (HFD) intake in the development of obesity still need to be elucidated. The ventromedial hypothalamus (VMH) is a major site involved in the regulation of glucose and energy homeostasis where “metabolic sensing neurons” integrate metabolic signals from the periphery. Among these signals, fatty acids (FA) modulate the activity of VMH neurons using the FA translocator/CD36, which plays a critical role in the regulation of energy and glucose homeostasis. During low-fat diet (LFD) intake, FA are oxidized by VMH astrocytes to fuel their ongoing metabolic needs. However, HFD intake causes VMH astrocytes to use FA to generate ketone bodies. We postulate that these astrocyte-derived ketone bodies are exported to neurons where they produce excess ATP and reactive oxygen species, which override CD36-mediated FA sensing and act as a signal to decrease short-term food intake. On a HFD, VMH astrocyte-produced ketones reduce elevated caloric intake to LFD levels after 3 days in rats genetically predisposed to resist (DR) diet-induced obesity (DIO), but not leptin-resistant DIO rats. This suggests that, while VMH ketone production on a HFD can contribute to protection from obesity, the inherent leptin resistance overrides this inhibitory action of ketone bodies on food intake. Thus, astrocytes and neurons form a tight metabolic unit that is able to monitor circulating nutrients to alter food intake and energy homeostasis.

Feeding and temperature responses to intravenous leptin infusion are differential predictors of obesity in rats

2004 ◽  
Vol 286 (4) ◽  
pp. R756-R763 ◽  
Author(s):  
Marie-Pierre Ruffin ◽  
Tiziana Adage ◽  
Folkert Kuipers ◽  
Jan H. Strubbe ◽  
Anton J. W. Scheurink ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Caloric Intake ◽  
High Energy ◽  
Leptin Resistance ◽  
Variable Effect ◽  
Male Wistar Rats ◽  
Plasma Leptin

Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar rats (weighing between 330 and 360 g) received intravenous infusions of 20 μg leptin 2 h before dark (∼57 μg/kg rat). Relative to saline infusion, this caused a highly variable effect on food intake (ranging between -94 and +129%), with food intake suppression that appeared negatively correlated with HED-induced increases in body weight gain, caloric intake, adiposity, and plasma leptin levels. In contrast, leptin's thermogenic response was positively correlated to body weight gain linked to weights of viscera, but not to adiposity. Before HED exposure, leptin unexpectedly increased food intake in some rats (fi+, n = 8), whereas others displayed the normal reduction in food intake (fi-, n = 7). HED-exposed fi+ rats had higher plasma leptin levels, retroperitoneal fat pad weight, HED intake, and body weight gain than fi- and chow-fed rats. These parameters were also higher in HED-exposed fi- rats relative to chow rats, except for plasma leptin concentrations. It is concluded that leptin's reduced efficacy to suppress food intake could predict obesity on an HED. An unexpected orexigenic effect of leptin might potentially contribute to this as well.

scholarly journals Hindbrain glucagon-like peptide-1 neurons track intake volume and contribute to injection stress-induced hypophagia in meal-entrained rats

2016 ◽  
Vol 310 (10) ◽  
pp. R906-R916 ◽  
Author(s):  
Alison D. Kreisler ◽  
Linda Rinaman
Keyword(s):  
Food Intake ◽  
Potential Role ◽  
Liquid Diet ◽  
Neural Activation ◽  
Intracerebroventricular Injection ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diet Intake ◽  
Published Research ◽  
Diet Type

Published research supports a role for central glucagon-like peptide 1 (GLP-1) signaling in suppressing food intake in rodent species. However, it is unclear whether GLP-1 neurons track food intake and contribute to satiety, and/or whether GLP-1 signaling contributes to stress-induced hypophagia. To examine whether GLP-1 neurons track intake volume, rats were trained to consume liquid diet (LD) for 1 h daily until baseline intake stabilized. On test day, schedule-fed rats consumed unrestricted or limited volumes of LD or unrestricted volumes of diluted (calorically matched to LD) or undiluted Ensure. Rats were perfused after the test meal, and brains processed for immunolocalization of cFos and GLP-1. The large majority of GLP-1 neurons expressed cFos in rats that consumed satiating volumes, regardless of diet type, with GLP-1 activation proportional to intake volume. Since GLP-1 signaling may limit intake only when such large proportions of GLP-1 neurons are activated, a second experiment examined the effect of central GLP-1 receptor (R) antagonism on 2 h intake in schedule-fed rats. Compared with baseline, intracerebroventricular vehicle (saline) suppressed Ensure intake by ∼11%. Conversely, intracerebroventricular injection of vehicle containing GLP-1R antagonist increased intake by ∼14% compared with baseline, partly due to larger second meals. We conclude that GLP-1 neural activation effectively tracks liquid diet intake, that intracerebroventricular injection suppresses intake, and that central GLP-1 signaling contributes to this hypophagic effect. GLP-1 signaling also may contribute to satiety after large volumes have been consumed, but this potential role is difficult to separate from a role in the hypophagic response to intracerebroventricular injection.

Injection of muscimol into posterior hypothalamus blocks stress-induced tachycardia

1989 ◽  
Vol 257 (1) ◽  
pp. R246-R251 ◽  
Author(s):  
M. Lisa ◽  
E. Marmo ◽  
J. H. Wible ◽  
J. A. DiMicco
Keyword(s):  
Gaba Receptors ◽  
Potential Role ◽  
Hypothalamic Nucleus ◽  
Gamma Aminobutyric Acid ◽  
Similar Treatment ◽  
Cardiovascular Changes ◽  
Vehicle Treatment ◽  
Response To Stress ◽  
Posterior Hypothalamic Nucleus

We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.

scholarly journals A Comparison of Total Food Intake at a Personalised Buffet in People with Obesity, before and 24 Months after Roux-en-Y-Gastric Bypass Surgery

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3873
Author(s):  
Natasha Kapoor ◽  
Werd al Najim ◽  
Camilo Menezes ◽  
Ruth K Price ◽  
Colm O’Boyle ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Food Intake ◽  
Gastric Bypass Surgery ◽  
Caloric Intake ◽  
High Energy ◽  
Relative Increase ◽  
High Energy Density ◽  
Total Food Intake ◽  
Ad Libitum ◽  
Operative Assessment

Long-term reductions in the quantity of food consumed, and a shift in intake away from energy dense foods have both been implicated in the potent bariatric effects of Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised that relative to pre-operative assessment, a stereotypical shift to lower intake would be observed at a personalised ad libitum buffet meal 24 months after RYGB, driven in part by decreased selection of high energy density items. At pre-operative baseline, participants (n = 14) rated their preference for 72 individual food items, each of these mapping to one of six categories encompassing high and low-fat choices in combination with sugar, complex carbohydrate or and protein. An 18-item buffet meal was created for each participant based on expressed preferences. Overall energy intake was reduced on average by 60% at the 24-month buffet meal. Reductions in intake were seen across all six food categories. Decreases in the overall intake of all individual macronutrient groups were marked and were generally proportional to reductions in total caloric intake. Patterns of preference and intake, both at baseline and at follow-up appear more idiosyncratic than has been previously suggested by verbal reporting. The data emphasise the consistency with which reductions in ad libitum food intake occur as a sequel of RYGB, this being maintained in the setting of a self-selected ad libitum buffet meal. Exploratory analysis of the data also supports prior reports of a possible relative increase in the proportional intake of protein after RYGB.

scholarly journals Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

2016 ◽  
Vol 310 (2) ◽  
pp. E103-E115 ◽  
Author(s):  
Lionel Carneiro ◽  
Sarah Geller ◽  
Xavier Fioramonti ◽  
Audrey Hébert ◽  
Cendrine Repond ◽  
...  
Keyword(s):  
Food Intake ◽  
Ketone Body ◽  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Glucose Production ◽  
Body Level ◽  
Homeostasis Regulation ◽  
The Impact ◽  
Body Concentration

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

Suppression of food intake by intravenous nutrients and insulin in the baboon

1984 ◽  
Vol 247 (2) ◽  
pp. R393-R401 ◽  
Author(s):  
S. C. Woods ◽  
L. J. Stein ◽  
L. D. McKay ◽  
D. Porte
Keyword(s):  
Food Intake ◽  
Caloric Intake ◽  
Glucose Infusion ◽  
Base Line ◽  
Papio Cynocephalus ◽  
Insulin Levels ◽  
Daily Caloric Intake ◽  
Total Base ◽  
Regulate Food Intake

Intravenous nutrients were infused at 25 and 50% of total base-line daily caloric intake to determine the role of circulating factors on spontaneous food ingestion in young adult male baboons (Papio cynocephalus). Glucose infusion suppressed food intake (15.1%) when 25% of total calories was infused (P less than 0.05) and 41.8% when 50% of total calories was infused (P less than 0.05) for 14-21 days. Both infusions produced basal hyperglycemia (82-172 mg/dl during 25% glucose and 120-239 mg/dl during 50% glucose). Both infusions also caused an increase in circulating insulin (48.1-63.1 microU/ml during 25% glucose and 68.5-77.2 microU/ml during 50% glucose). The simultaneous infusion of exogenous insulin (0.33 mU X kg-1 X min-1) prevented hyperglycemia (85.8-87.9 mg/dl during 25% glucose) but maintained raised basal peripheral insulin levels (52.4-84.4 microU/ml). The 13% suppression of food intake (P less than 0.05) was similar to glucose infusion alone. Comparable infusions of Intralipid as 25 and 50% of total daily calories also suppressed spontaneous food intake but did not produce hyperglycemia or elevated insulin levels. The magnitude of suppression was similar to that of glucose: 16% when 25% of basal calories was infused (P less than 0.05) and 31.3% when 50% of basal calories was infused (P less than 0.05). However, the pattern was different with a more rapid effect, which tended to diminish in time, rather than the slow effect found with glucose, which was maintained for 14 days. We conclude that circulating nutrients can regulate food intake independent of gastrointestinal absorption in primates.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mario Caba ◽  
Enrique Meza ◽  
Carolina Escobar ◽  
Angeles Jiménez ◽  
Mario Daniel Caba-Flores ◽  
...  
Keyword(s):  
Food Intake ◽  
Hypothalamic Nucleus ◽  
Restricted Feeding ◽  
Adult Rats ◽  
Peripheral Oscillators ◽  
Food Anticipatory Activity ◽  
Ad Libitum ◽  
Anticipatory Activity ◽  
Oxytocinergic Cells

AbstractThe mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

scholarly journals Oxytocinergic Cells of the Posterior Hypothalamic Paraventricular Nucleus Participate in the Food Entrained Clock

2021 ◽  
Author(s):  
Mario Caba ◽  
Enrique Meza ◽  
Carolina Escobar ◽  
Angeles Jiménez ◽  
Mario Daniel Caba-Flores ◽  
...  
Keyword(s):  
Food Intake ◽  
Hypothalamic Nucleus ◽  
Restricted Feeding ◽  
Adult Rats ◽  
Peripheral Oscillators ◽  
Food Anticipatory Activity ◽  
Ad Libitum ◽  
Anticipatory Activity ◽  
Oxytocinergic Cells

Abstract The mechanisms underlying food anticipatory activity is still not well understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON) and in the medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), Ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or Ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; contrasting, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

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