scholarly journals Leptin-induced increase in body fat content of rats

2013 ◽  
Vol 304 (3) ◽  
pp. E267-E281 ◽  
Author(s):  
Ruth B. S. Harris
Keyword(s):  
Food Intake ◽  
Energy Intake ◽  
Body Fat ◽  
Leptin Receptor ◽  
Sucrose Solution ◽  
Third Ventricle ◽  
Maximal Response ◽  
Lean Tissue ◽  
Leptin Receptors ◽  
Reduced Body

We previously reported that peripheral leptin infusions in chronically decrebrate rats, in which the forebrain is neurally isolated from the hindbrain, increased body fat and decreased energy expenditure. Any central leptin response in decerebrate rats would depend upon the hindbrain. Here, we tested whether selective activation of hindbrain leptin receptors increased body fat. Fourth ventricle infusion of 0.6 μg leptin/day for 12 days increased body fat by 13% with no increase in food intake. Third ventricle leptin infusions decreased food intake, body fat, and lean tissue with a maximal response at 0.3 μg leptin/day. To test whether hindbrain receptors opposed activity of hypothalamic receptors, rats received peripheral infusions of 40 μg leptin/day and increasing 4th ventricle doses of the leptin receptor antagonist mutein protein. Mutein (3.0 μg/day) reduced body fat in PBS-infused rats to the same level as leptin-infused rats and reduced lean tissue in all rats. Leptin, but not mutein, inhibited food intake. By contrast, 3.0 μg/day mutein in the 3rd ventricle increased food intake and body fat in both PBS- and leptin-infused rats. In basal conditions, hindbrain leptin receptors may antagonize activity of forebrain receptors to protect lean and fat tissue, but there is no evidence for an anabolic role for hindbrain receptors when leptin is elevated. In a dietary study, rats increased energy intake when offered lard and 30% sucrose solution in addition to chow. Peripheral leptin infusion exaggerated the gain in body fat without altering energy intake confirming the potential for leptin to increase adiposity.

Leptin action is modified by an interaction between dietary fat content and ambient temperature

2004 ◽  
Vol 287 (5) ◽  
pp. R1250-R1255 ◽  
Author(s):  
Andrea L. Haltiner ◽  
Tiffany D. Mitchell ◽  
Ruth B. S. Harris
Keyword(s):  
Energy Intake ◽  
Body Fat ◽  
Dietary Fat ◽  
Leptin Receptor ◽  
Environmental Temperature ◽  
Short Form ◽  
Uncoupling Protein ◽  
Fat Content ◽  
High Fat ◽  
Leptin Receptors

Mice adapted to a high-fat diet are reported to be leptin resistant; however, we previously reported that mice fed a high-fat (HF) diet and housed at 23°C remained sensitive to peripheral leptin and specifically lost body fat. This study tested whether leptin action was impaired by a combination of elevated environmental temperature and a HF diet. Male C57BL/6 mice were adapted to low-fat (LF) or HF diet from 10 days of age and were housed at 27°C from 28 days of age. From 35 days of age, baseline food intake and body weight were recorded for 1 wk and then mice on each diet were infused with 10 μg leptin/day or PBS from an intraperitoneal miniosmotic pump for 13 days. HF-fed mice had a higher energy intake than LF-fed mice and were heavier but not fatter. Serum leptin was lower in PBS-infused HF- than LF-fed mice. Leptin significantly inhibited energy intake of both LF-fed and HF-fed mice, and this was associated with a significant increase in hypothalamic long-form leptin receptors with no change in short-form leptin receptor or brown fat uncoupling protein-1 mRNA expression. Leptin significantly inhibited weight gain in both LF- and HF-fed mice but reduced the percentage of body fat mass only in LF-fed mice. The percentage of lean and fat tissue in HF-fed mice did not change, implying that overall growth had been inhibited. These results suggest that dietary fat modifies the mechanisms responsible for leptin-induced changes in body fat content and that those in HF-fed mice are sensitive to environmental temperature.

scholarly journals Blockade of the cerebral aqueduct in rats provides evidence of antagonistic leptin responses in the forebrain and hindbrain

2014 ◽  
Vol 306 (4) ◽  
pp. E414-E423 ◽  
Author(s):  
Michael I. Vaill ◽  
Bhavna N. Desai ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Body Fat ◽  
Fourth Ventricle ◽  
Third Ventricle ◽  
Cerebral Aqueduct ◽  
Sprague Dawley ◽  
Leptin Receptors ◽  
The Third ◽  
Inhibit Food Intake

Previously, we reported that low-dose leptin infusions into the fourth ventricle produced a small but significant increase in body fat. These data contrast with reports that injections of higher doses of leptin into the fourth ventricle inhibit food intake and weight gain. In this study, we tested whether exogenous leptin in the fourth ventricle opposed or contributed to weight loss caused by third ventricle leptin infusion by blocking diffusion of CSF from the third to the fourth ventricle. Male Sprague-Dawley rats received third ventricle infusions of PBS or 0.3 μg leptin/24 h from miniosmotic pumps. After 4 days, rats received a 3-μl cerebral aqueduct injection of saline or of thermogelling nanoparticles (hydrogel) that solidified at body temperature. Third ventricle leptin infusion inhibited food intake and caused weight loss. Blocking the aqueduct exaggerated the effect of leptin on food intake and weight loss but had no effect on the weight of PBS-infused rats. Leptin reduced both body fat and lean body mass but did not change energy expenditure. Blocking the aqueduct decreased expenditure of rats infused with PBS or leptin. Infusion of leptin into the third ventricle increased phosphorylated STAT3 in the VMHDM of the hypothalamus and the medial NTS in the hindbrain. Blocking the aqueduct did not change hypothalamic p-STAT3 but decreased p-STAT3 in the medial NTS. These results support previous observations that low-level activation of hindbrain leptin receptors has the potential to blunt the catabolic effects of leptin in the third ventricle.

scholarly journals Low-dose infusions of leptin into the nucleus of the solitary tract increase sensitivity to third ventricle leptin

2019 ◽  
Vol 316 (5) ◽  
pp. E719-E728 ◽  
Author(s):  
Ruth B. S. Harris
Keyword(s):  
Food Intake ◽  
Fourth Ventricle ◽  
Low Dose ◽  
Third Ventricle ◽  
Solitary Tract ◽  
Neural Pathway ◽  
Leptin Receptors ◽  
Reduced Body ◽  
Neural Connection ◽  
Cumulative Intake

Previous studies suggest that weight loss occurs when leptin receptors in both the forebrain and hindbrain are activated. Experiments described here tested whether this integration is mediated through a neural connection or by leptin diffusion through the subarachanoid space. If the hypothalamus and hindbrain communicated through a neural pathway, then a very low dose of leptin infused directly into the nucleus of the solitary tract (NTS) would enhance the response to third ventricle (3V) leptin but would have no effect if infused into the fourth ventricle (4V). A 12-day infusion of 10 ng/24 h into the 4V or the NTS reduced body fat. Leptin at 5 ng/24 h into the 4V or NTS had no effect on food intake or body composition, but infusion of 5 ng of leptin/24 h into the NTS combined with a 3V injection of 0.1 μg of leptin inhibited food intake between 6 and 12 h after injection. Cumulative intake was inhibited for up to 36 h. 3V leptin had no effect on food intake of rats receiving the 4V leptin infusion. Similar results were found using infusions of 5 ng leptin/24 h and a 3V injection of 0.025 μg leptin. These data suggest that activation of leptin receptors in the NTS lowers the threshold for response to leptin in the forebrain through a neural network.

Metabolic responses to leptin in obese db/db mice are strain dependent

2001 ◽  
Vol 281 (1) ◽  
pp. R115-R132 ◽  
Author(s):  
Ruth B. S. Harris ◽  
Tiffany D. Mitchell ◽  
Xiaolang Yan ◽  
Jacob S. Simpson ◽  
Stephen M. Redmann
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Fat ◽  
Leptin Receptor ◽  
Short Form ◽  
Fasting Blood Glucose ◽  
Male Mice ◽  
Background Strain ◽  
Reduced Body ◽  
Intraperitoneal Infusion

Obese, diabetic C57BL/Ks db/db mice that lack the long-form leptin receptor exhibit no decrease in body weight or food intake when treated with leptin. Here we compared responses to leptin in two strains of db/db mice: C57BL/6J mice that are hyperglycemic and hyperinsulinemic and C57BL/Ks that are hyperglycemic and normo- or hypoinsulinemic. Chronic intraperitoneal infusion of 10 μg leptin/day partially reversed hyperglycemia in C57BL/6J male mice but exaggerated the diabetic state of female mice. Bolus intraperitoneal injections of 40 μg leptin/day did not effect glucose in either strain of male db/db mice, whereas chronic intraperitoneal infusion of 20 μg leptin/day significantly reduced fasting blood glucose in male mice from both strains, especially C57BL/6J mice. Food intake, body weight, rectal temperature, and body fat did not change. Chronic intraperitoneal infusion of 10 μg leptin/day significantly reduced body fat in lean db/+ C57BL/6J but not in C57BL/Ks mice. Thus peripherally administered leptin is active in mice that have only short-form leptin receptors, and the response is dependent on the method of leptin administration and the background strain.

scholarly journals Antiobesity Effects of the β-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5855-5864 ◽  
Author(s):  
Jonathan D. Roth ◽  
Heather Hughes ◽  
Eric Kendall ◽  
Alain D. Baron ◽  
Christen M. Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Respiratory Quotient ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Lean Tissue ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Cell Hormone

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 μg/kg·d, 22d) reduced food intake and slowed weight gain: approximately 10% (P < 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P < 0.05). Whereas PF decreased lean tissue (P < 0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean ± se, 0.82 ± 0.0, 0.81 ± 0.0, respectively; P < 0.05) similar to VEH (0.84 ± 0.01). Energy expenditure (EE mean ± se) tended to be reduced by PF (5.67 ± 0.1 kcal/h·kg) and maintained by amylin (5.86 ± 0.1 kcal/h·kg) relative to VEH (5.77 ± 0.0 kcal/h·kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74 ± 0.09 kcal/·kg; P < 0.05) relative to VEH (5.49 ± 0.06) and PF (5.38 ± 0.07 kcal/h·kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P < 0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P < 0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.

Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake

1999 ◽  
Vol 276 (4) ◽  
pp. R1172-R1179 ◽  
Author(s):  
James P. DeLany ◽  
Fawn Blohm ◽  
Alycia A. Truett ◽  
Joseph A. Scimeca ◽  
David B. West
Keyword(s):  
Body Composition ◽  
Linoleic Acid ◽  
Food Intake ◽  
Conjugated Linoleic Acid ◽  
Energy Intake ◽  
Body Fat ◽  
Metabolic Effects ◽  
Protein Accumulation ◽  
High Fat ◽  
Fat Accumulation

Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects on body fat accumulation. In our previous work, CLA reduced body fat accumulation in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced energy intake, the results suggested that some of the metabolic effects were not a consequence of the reduced food intake. We therefore undertook a study to determine a dose of CLA that would have effects on body composition without affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by weight) were studied in AKR/J male mice ( n = 12/group; age, 39 days) maintained on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups compared with controls. The retroperitoneal depot was most sensitive to the effects of CLA, whereas the epididymal depot was relatively resistant. Higher doses of CLA also significantly increased carcass protein content. A time-course study of the effects of 1% CLA on body composition showed reductions in fat pad weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion, CLA feeding produces a rapid, marked decrease in fat accumulation, and an increase in protein accumulation, at relatively low doses without any major effects on food intake.

A note on the effects of body fatness and level of food intake on the rate of fat loss in lactating ewes

1982 ◽  
Vol 34 (3) ◽  
pp. 355-357 ◽  
Author(s):  
R. T. Cowan ◽  
J. J. Robinson ◽  
I. McDonald
Keyword(s):  
Food Intake ◽  
Energy Intake ◽  
Body Fat ◽  
Metabolizable Energy ◽  
Body Fatness ◽  
Fat Loss ◽  
Body Fat Content ◽  
Metabolizable Energy Intake ◽  
Image Position ◽  
The Relationship

ABSTRACTData from three comparative slaughter experiments involving a total of 73 ewes were used to study the influence of body fat content at the start of lactation (X1 kg) and of metabolizable energy intake (X2, MJ/day), on the rate of loss of body fat by lactating ewes over the first 6 weeks of lactation (Y, g/day). The relationship was described by the equation:Thus the rate of fat loss was greater for ewes with higher initial fat contents, but the differential became less as metabolizable energy intake increased. Since increases in body fatness depress food intake it was not possible to prevent loss of body fat during early lactation in fat ewes given high concentrate diets ad libitum. The likely response in milk yield to increase in body fatness at parturition is therefore strongly dependent on the relative levels of body fatness and metabolizable energy intake. The value of any improvement in condition of the ewe at parturition may be considerable when metabolizable energy intake during lactation is low but much less when it is expected to be high.

scholarly journals Inconsistencies in the assessment of food intake

2012 ◽  
Vol 303 (12) ◽  
pp. E1408-E1418 ◽  
Author(s):  
Stephen C. Woods ◽  
Wolfgang Langhans
Keyword(s):  
Food Intake ◽  
Energy Intake ◽  
Body Fat ◽  
Energy Homeostasis ◽  
Behavioral Responses ◽  
Normal Function ◽  
Direct Proportion ◽  
Heated Debate ◽  
The Brain ◽  
Reducing Energy

Many peptides and other compounds that influence metabolism also influence food intake, and numerous hypotheses explaining the observed effects in terms of energy homeostasis have been suggested over the years. For example, cholecystokinin (CCK), a duodenal peptide secreted during meals that aids in digestion, also reduces ongoing food intake, thereby contributing to satiation; and insulin and leptin, hormones secreted in direct proportion to body fat, act in the brain to help control adiposity by reducing energy intake. These behavioral actions are often considered to be hard-wired, such that negative experiments, in which an administered compound fails to have its purported effect, are generally disregarded. In point of fact, failures to replicate the effects of compounds on food intake are commonplace, and this occurs both between and within laboratories. Failures to replicate have historically fueled heated debate about the efficacy and/or normal function of one or another compound, leading to confusion and ambiguity in the literature. We review these phenomena and their implications and argue that, rather than eliciting hard-wired behavioral responses in the maintenance of homeostasis, compounds that alter food intake are subjected to numerous influences that can render them completely ineffective at times and that a major reason for this variance is that food intake is not under stringent homeostatic control.

Eating traits in relation to performance and carcass traits of restrictedly fed group-housed finishing pigs

1999 ◽  
Vol 68 (3) ◽  
pp. 399-405 ◽  
Author(s):  
P. J. L. Ramaekers ◽  
J. W. G. M. Swinkels ◽  
J. H. Huiskes ◽  
M. W. A. Verstegen
Keyword(s):  
Food Intake ◽  
Energy Intake ◽  
Carcass Traits ◽  
Live Weight ◽  
Free Access ◽  
Daily Energy Intake ◽  
Lean Tissue ◽  
Tissue Content ◽  
Daily Energy ◽  
Ad Libitum

AbstractSeventy-two crossbred barrows (28.7 ± 0.3 kg live weight (LW)) were used to examine whether there is a relation between eating traits, and performance and carcass traits in ad libitum and restrictedly fed group-housed pigs. The experiment included two replicates, each consisting of 36 pigs. From day 1 to 42, all pigs were maintained with free access to a starter diet containing 12.7 MJ metabolizable energy (ME) and 8.2 g ileal apparent digestible lysine per kg. The experimental period was from day 42 (55.9 kg LW) to the end of the experiment (110.2 kg LW). The pigs in treatment 1 were maintained with free access to a high (H) energy diet (13.1 MJ ME and 7.1 g ileal apparent digestible lysine per kg). For pigs in treatments 2 and 3 the daily energy allowance per pig was restricted to 18 MJ ME above the daily energy requirement for maintenance using diet H, and a low (L) energy diet (12.5 MJ ME and 6.7 g ileal apparent digestible lysine per kg), respectively. The weekly measured LW was used to compute the energy requirements for maintenance (M = 0·719 MJ ME × LW (kg)0.63). Daily food intake and eating traits per pig were determined using transponders and an electronic feeding station equipped with an antenna.Daily energy intake of the ad libitum and restrictedly fed pigs was correlated with growth and lean meat tissue content of the carcass. In the pigs given food ad libitum, daily energy intake was correlated with daily feeder visiting time, time per meal and food intake per meal, but not with number of meals per day and rate of food intake. In the restricted treatments, number of meals per day was correlated with energy intake, but not with lean tissue content of the carcass. In conclusion, number of meals per day explained part of the variation of lean tissue content of the carcass in ad libitum, but not in restrictedly fed group-housed pigs.

scholarly journals Integrated Effects of Leptin in the Forebrain and Hindbrain of Male Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2663-2675 ◽  
Author(s):  
Bhavna N. Desai ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Body Fat ◽  
Fourth Ventricle ◽  
Third Ventricle ◽  
Male Rats ◽  
Low Doses ◽  
Sprague Dawley ◽  
The Third ◽  
Stat3 Phosphorylation

Abstract Leptin receptors (ObRs) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. It is unclear how leptin activity in these areas is integrated. We tested whether both forebrain and hindbrain ObRs have to be activated simultaneously to change energy balance and to maintain metabolic homeostasis. Previous studies used acute leptin injections in either the third ventricle (1–5 μg) or the fourth ventricle (3–10 μg); here we used 12-day infusions of low doses of leptin in one or both ventricles (0.1 μg/24 h in third, 0.6 μg/24 h in fourth). Male Sprague Dawley rats were fitted with third and fourth ventricle cannulas, and saline or leptin was infused from Alzet pumps for 6 or 12 days. Rats that received leptin into only the third or the fourth ventricle were not different from controls that received saline in both ventricles. By contrast, rats with low-dose leptin infusions into both the third and fourth ventricle showed a dramatic 60% reduction in food intake that was reversed on day 6, a 20% weight loss that stabilized on day 6, and a 50% decrease in body fat at day 12 despite the correction of food intake. They displayed normal activity and maintained energy expenditure despite weight loss, indicating inappropriately high thermogenesis that coincided with increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in the brainstem. Altogether, these findings show that with low doses of leptin, chronic activation of both hypothalamic and brainstem ObRs is required to reduce body fat.

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