Chronic Stimulation of Leptin on Food Intake and Body Weight after Microinjection into the Ventromedial Hypothalamus of Conscious Rats

A very low dose of leptin (50 ng) was microinjected into the ventro-medial hypothalamus (VMH) of each rat daily once for three days. Food intake and body weight were measured after leptin injections. Microinjection of leptin into the VMH reduced food intake by 33.3 % significantly (P<0.01) during three days of leptin injection compared to the control. Body weight was measured after 24 h, 48 h and 72 h of leptin injection. After 24 h (P<0.01) and 48 h (P<0.05) of leptin injection, body weight was reduced significantly compared to that of rat before injection. Similarly, after 72 h of leptin injection, a significant reduced body weight was observed (P<0.1). A significant (P<0.001) reduced changes of body weight were found after 24 h, 48 h and 72 h after injection into the VMH when compared to the respective controls injected with saline. The results suggest that leptin has dramatic effect on reducing body weight by inhibition of food intake. doi: 10.3329/taj.v19i2.3154 TAJ 2006; 19(2): 70-75

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Mechanisms of Amylin/Leptin Synergy in Rodent Models

Endocrinology ◽

10.1210/en.2009-0546 ◽

2010 ◽

Vol 151 (1) ◽

pp. 143-152 ◽

Cited By ~ 91

Author(s):

Victoria F. Turek ◽

James L. Trevaskis ◽

Barry E. Levin ◽

Ambrose A. Dunn-Meynell ◽

Boman Irani ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Leptin Receptor ◽

Therapeutic Potential ◽

Ventromedial Hypothalamus ◽

Signal Transducer ◽

Leptin Signaling ◽

Reduced Body ◽

Epididymal Fat ◽

Transcription 3

Abstract The present studies aimed to identify mechanisms contributing to amylin/leptin synergy in reducing body weight and adiposity. We reasoned that if amylin/leptin harnessed complementary neuronal pathways, then in the leptin-sensitive state, amylin should augment leptin signaling/binding and that in the absence of endogenous amylin, leptin signaling should be diminished. Amylin (50 μg/kg, ip) amplified low-dose leptin-stimulated (15 μg/kg, ip) phosphorylated signal transducer and activator of transcription-3 signaling within the arcuate nucleus (ARC) in lean rats. Amylin (50 μg/kg · d) or leptin (125 μg/kg · d) infusion to lean rats decreased 28-d food intake (14 and 10%, respectively), body weight (amylin by 4.3%, leptin by 4.9%), and epididymal fat (amylin by 19%, leptin by 37%). Amylin/leptin co-infusion additively decreased food intake (by 26%) and reduced body weight (by 15%) and epididymal fat (by 78%; all P < 0.05 vs. all groups) in a greater than mathematically additive manner, consistent with synergy. Amylin increased leptin binding within the ventromedial hypothalamus (VMN) by 35% and dorsomedial hypothalamus by 47% (both P < 0.05 vs. vehicle). Amylin/leptin similarly increased leptin binding in the VMN by 40% and ARC by 70% (P < 0.05 vs. vehicle). In amylin-deficient mice, hypothalamic leptin receptor mRNA expression was reduced by 50%, leptin-stimulated phosphorylated signal transducer and activator of transcription-3 within ARC and VMN was reduced by 40%, and responsiveness to leptin’s (1 mg/kg · d for 28 d) weight-reducing effects was attenuated (all P < 0.05 vs. wild-type controls). We suggest that amylin/leptin’s marked weight- and fat-reducing effects are due to activation of intrinsic synergistic neuronal signaling pathways and further point to the integrated neurohormonal therapeutic potential of amylin/leptin agonism in obesity.

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Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.2.r563 ◽

1997 ◽

Vol 272 (2) ◽

pp. R563-R569 ◽

Cited By ~ 19

Author(s):

L. R. Leon ◽

W. Kozak ◽

J. Peschon ◽

M. J. Kluger

Keyword(s):

Body Weight ◽

Food Intake ◽

Motor Activity ◽

Knockout Mice ◽

Low Dose ◽

Late Phase ◽

High Dose ◽

Wild Type ◽

Inflammatory Stimuli ◽

Necrosis Factor

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.

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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 ◽

10.1210/en.2006-0393 ◽

2006 ◽

Vol 147 (12) ◽

pp. 5855-5864 ◽

Cited By ~ 114

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.

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Pulmonary delivery of peptide YY for food intake suppression and reduced body weight gain in rats

Diabetes Obesity and Metabolism ◽

10.1111/j.1463-1326.2011.01363.x ◽

2011 ◽

Vol 13 (5) ◽

pp. 408-417 ◽

Cited By ~ 12

Author(s):

P. P. Nadkarni ◽

R. M. Costanzo ◽

M. Sakagami

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Peptide Yy ◽

Body Weight Gain ◽

Pulmonary Delivery ◽

Reduced Body

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Low Dose Leptin Administration Reverses Effects of Sustained Weight-Reduction on Energy Expenditure and Circulating Concentrations of Thyroid Hormones

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.87.5.8628 ◽

2002 ◽

Vol 87 (5) ◽

pp. 2391-2394 ◽

Cited By ~ 188

Author(s):

Michael Rosenbaum ◽

Ellen M. Murphy ◽

Steven B. Heymsfield ◽

Dwight E. Matthews ◽

Rudolph L. Leibel

Keyword(s):

Body Composition ◽

Body Weight ◽

Energy Expenditure ◽

Thyroid Hormones ◽

Low Dose ◽

Total Energy Expenditure ◽

Metabolic Phenotype ◽

Time Points ◽

Reduced Body ◽

Reduced State

Maintenance of a reduced body weight is associated with decreased 24-hour energy expenditure, and decreased circulating concentrations of leptin and thyroid hormones. To determine whether these adaptive metabolic and endocrine changes are partly leptin-mediated, we measured body composition, aspects of energy expenditure, and circulating concentrations of leptin and thyroid hormones in 4 subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced body weight; and 3.) During a 5-week period at 10% reduced body weight while receiving twice per day leptin injections that restored 8 AM circulating leptin concentrations to those seen at usual body weight. During maintenance of a 10% reduced body weight, circulating T3, T4, and leptin concentrations were decreased. All of these endocrine changes were reversed by administration of “replacement” doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle changes in body composition associated with leptin administration, were used to calculate the net change in stored calories and in 24-hour energy expenditure. Total energy expenditure increased in all subjects during r-metHuLeptin administration. These data indicate that decrease leptin concentrations resulting from loss of fat mass account for some aspects of the endocrine/metabolic phenotype associated with the weight-reduced state.

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Failure to demonstrate disruption of ultradian growth hormone rhythm and insulin secretion by dorsomedial hypothalamic nucleus lesions that cause reduced body weight, linear growth and food intake

Experimental Brain Research ◽

10.1007/bf00270690 ◽

1987 ◽

Vol 66 (3) ◽

pp. 572-576 ◽

Cited By ~ 15

Author(s):

L. L. Bernardis ◽

G. S. Tannenbaum

Keyword(s):

Growth Hormone ◽

Body Weight ◽

Insulin Secretion ◽

Food Intake ◽

Linear Growth ◽

Hypothalamic Nucleus ◽

Reduced Body ◽

Dorsomedial Hypothalamic Nucleus

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Stimulation of food intake after central galanin is associated with arcuate nucleus activation and does not differ between genetically selected low and high body weight lines of chickens

Neuropeptides ◽

10.1016/j.npep.2012.11.003 ◽

2013 ◽

Vol 47 (4) ◽

pp. 281-285 ◽

Cited By ~ 11

Author(s):

Christopher J. Hagen ◽

Brandon A. Newmyer ◽

Rebekah I. Webster ◽

Elizabeth R. Gilbert ◽

Paul B. Siegel ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Arcuate Nucleus ◽

High Body Weight ◽

High Body ◽

Stimulation Of

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Acute and chronic gastrin-releasing peptide decreases food intake in baboons

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1985.248.5.r578 ◽

1985 ◽

Vol 248 (5) ◽

pp. R578-R583 ◽

Cited By ~ 1

Author(s):

D. P. Figlewicz ◽

L. J. Stein ◽

S. C. Woods ◽

D. Porte

Keyword(s):

Insulin Secretion ◽

Food Intake ◽

Basal Insulin ◽

Low Dose ◽

Chronic Administration ◽

Gastrin Releasing Peptide ◽

Total Food Intake ◽

Total Food ◽

Basal Insulin Secretion ◽

Stimulation Of

Gastrin-releasing peptide (GRP) is a peptide structurally related to bombesin that appears to be localized to the mammalian gastrointestinal tract. This study examined the ability of GRP, when administered on either an acute or chronic basis, to suppress food intake in baboons. When administered at 8 micrograms/kg iv before a morning meal, GRP significantly suppressed both food intake and the postprandial rise of plasma glucose and insulin. GRP at doses of 1, 2, 4, and 8 micrograms/kg stimulated basal insulin secretion. Chronic administration of GRP (q.o.d. for 11 days) at a low dose before the A.M. meal resulted in suppression of the A.M. meal and an initial suppression of total food intake, which recovered before the end of the treatment period. In conclusion, GRP appears to be effective in acute suppression of food intake and stimulation of basal insulin secretion in the nonhuman primate.

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PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00726.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. R367-R375 ◽

Cited By ~ 86

Author(s):

Niels Vrang ◽

Andreas Nygaard Madsen ◽

Mads Tang-Christensen ◽

Gitte Hansen ◽

Philip Just Larsen

Keyword(s):

Body Weight ◽

Food Intake ◽

Peptide Yy ◽

Body Weight Gain ◽

Subcutaneous Administration ◽

Treated Group ◽

Metabolic Effects ◽

Male Rats ◽

Reduced Body ◽

Gut Hormone

The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3–36) in mice and rats, as well as metabolic effects of chronic PYY(3–36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3–36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 μg·kg−1·day−1) of PYY(3–36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 μg·kg−1·day−1) of PYY(3–36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 μg·kg−1·day−1 PYY(3–36) weighed ∼10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3–36) (250 and 1,000 μg·kg−1·day−1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 μg/kg PYY(3–36) elicited a conditioned taste aversion in male rats.

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