The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index; none of the 85 sources its claims cite is checked for support yet.
Leptin at 14 y of age: an ongoing story
Open accessAbstract
The cloning of the ob gene and its gene product leptin has led to the elucidation of a robust physiologic system that maintains constancy of fat stores. Leptin is a peptide hormone secreted by adipose tissue and regulates adipose tissue mass and energy balance. Recessive mutations in the leptin gene are associated with massive obesity in mice and in some humans, which establishes a genetic basis for obesity. Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure. When fat mass decreases, plasma leptin concentrations decrease, which stimulates appetite and suppresses energy expenditure until fat mass is restored. When fat mass increases, leptin concentrations increase, which suppresses appetite until weight is lost. This system maintains homeostatic control of adipose tissue mass.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review summarizes 14 years of leptin research, describing leptin as an adipose-derived hormone in a negative feedback loop that regulates fat mass and energy balance, with leptin deficiency syndromes treatable by replacement. It argues that most obesity involves leptin resistance and that leptin provides a biological basis for obesity, while noting limited efficacy as monotherapy in unselected obese patients.
Key findings
- Leptin circulates as an ~16-kD protein; concentrations rise and fall with adipose mass, and recombinant leptin reduces food intake and body weight in wild-type and ob mice but not db mice, establishing receptor specificity.
- Leptin replacement improves leptin deficiency syndromes including congenital leptin deficiency, lipodystrophy, and hypothalamic amenorrhea; hypothalamic amenorrhea affects 4–8% of women of reproductive age and accounts for as many as 1 in 3 visits by women to an infertility clinic (personal communication).
- Most obese patients are leptin resistant: in a small cohort, only ~1/3 showed clinically significant weight loss with leptin therapy, and ~10–15% of obese subjects have leptin concentrations indistinguishable from lean patients. Leptin plus amylin produced 12.9% weight loss, significantly greater than either agent alone.
- Single-gene Mendelian defects account for ~8% or more of morbid human obesity, and twin studies indicate a heritability of 0.7–0.9 for obesity.
Methods
- Narrative review/symposium article presented at “Leptin: Weight Management and Beyond,” Experimental Biology 2008; it synthesizes published animal and human literature.
- No primary data collection, systematic search strategy, or formal quantitative analysis is described; the paper includes cited personal communications and references.
Limitations
- No explicit limitations section is provided. Evident from the text: this is a non-systematic narrative review whose conclusions rely on selected studies and personal communications rather than a systematic search.
- The paper states that it is yet unclear whether obese individuals who respond to leptin have lower starting leptin concentrations than nonresponders, and that the possibility of leptin efficacy in obese patients with low plasma leptin concentrations “has not been directly tested in humans.”
- The molecular mechanism by which amylin ameliorates leptin resistance “has not been fully established.”
Model-written summary. Check it against the paper before relying on it.
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Verification
Claims the paper makes
63 Not checked yet · 22 Own interpretation · 9 No basis given · 1 Own result
In the paper
“The weight of animals that were either overfed or starved returned to that of a control group once the stimulus to alter weight was removed (2,(7)(8)(9)(10)(11).”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites (2,(7)(8)(9)(10)(11)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“These mutant mice show an identical phenotype to animals with null mutations of the leptin receptor or leptin itself (25,26).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“food intake and body weight-or, more precisely, adipose tissue mass-were regulated by an endocrine system.”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“ObRb was highly enriched in the hypothalamus in precisely those nuclei that alter body weight when lesioned (25,27).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a circulating factor produced in adipose tissue and encoded by the ob gene acted on a receptor in the hypothalamus that was encoded by the db locus.”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“when animals are fed nutrients in varying dilutions, they adjust their intake to maintain constancy of the number of calories that are consumed, not the volume (12).”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites [12] Adolph, 1947, Urges to eat and drink in rats., Am J Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“ObRb is the only receptor isoform that expresses all the protein motifs required for cytokine receptor signaling.”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“a precise balance between energy intake and energy expenditure has been noted over even a 2wk time frame, which tended to average out day-to-day fluctuations in intake (6).”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites [6] Edholm, 1955, The energy expenditure and food intake of individual men., Br J Nutr source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This system maintains homeostatic control of adipose tissue mass.”
§ Leptin at 14 y of age: an ongoing story 1-4 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“this polypeptide, now known as leptin (from the Greek root leptos, meaning ''thin''), functioned as the afferent signal in a negative feedback loop that maintained stability of adipose tissue mass (1)(2)(3)(4).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
- Not checked yetcites (1)(2)(3)(4)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 21
- It may state two separate claims as one. 28
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“When fat mass increases, leptin concentrations increase, which suppresses appetite until weight is lost.”
§ Leptin at 14 y of age: an ongoing story 1-4 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This RNA encoded a predicted 167-amino acid polypeptide with a signal sequence, which indicated that it was secreted and likely to circulate in plasma.”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The phenotypes of both mutations are strikingly similar, which suggests that the encoded genes function in the same physiologic pathway.”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The leptin receptor was identifiedbiochemically and shown tobe a cytokine family receptor that is expressed broadly (24).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
- Not checked yetcites [24] Tartaglia, 1995, Identification and expression cloning of a leptin receptor, OB-R., Cell source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Leptin concentrations increase with accretion of adipose tissue mass and decrease when adipose mass is lost (22).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
- Not checked yetcites [22] Maffei, 1995, Leptin levels in human and rodent: measurement of plasma leptin andob RNA in obese and weight-reduced subjects., Nat Med source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure.”
§ Leptin at 14 y of age: an ongoing story 1-4 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“brain centers in the hypothalamus receive peripheral signals that reflect an organism's nutritional state as part of a feedback loop or loops that maintain homeostatic control of body weight (14,15).”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites [14] Brobeck, 1946, Mechanism of the development of obesity in animals with hypothalamic lesions., Physiol Rev source
- Not checked yetcites [15] Mayer, 1955, Regulation of energy intake and the body weight: the glucostatic theory and the lipostatic hypothesis., Ann NY Acad Sci source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The failure of recombinant leptin to alter food intake or weight in db mice established the specificity of the effect and essentially excluded the possibility that the protein reduced weight as a result of an aversive effect (2).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
- Not checked yetcites [2] Halaas, 1995, Weight-reducing effects of the plasma protein encoded by the obese gene., Science source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“All these data suggested that there must be a biological system that regulates food intake and maintains homeostatic control of body weight (12).”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites [12] Adolph, 1947, Urges to eat and drink in rats., Am J Physiol source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Results from parabiosis experiments were consistent with this possibility and further suggested that the ob gene encoded a circulating factor that suppressed food intake and body weight and that the db gene encoded its receptor.”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It was subsequently shown that leptin receptor RNA was alternatively spliced and that only one of the splice variants, referred to as ObRb at the time (also known as LepR-l), was mutant in C57Bl/Ks db/db mice (25,26).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The ob gene was cloned in 1994, and leptin was identified in 1995 as the product of the ob gene and a hormonal signal that regulates energy balance (1)(2)(3)(4).”
§ Leptin at 14 y of age: an ongoing story 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites (1)(2)(3)(4)
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“body weight could be altered, in either direction, by introducing specific lesions in the hypothalamus in which ventromedial hypothalamic lesions caused obesity and lateral hypothalamic lesions caused leanness (13).”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites [13] Hetherington, 1942, The spontaneous activity and food intake of rats with hypothalamic lesions., Am J Physiol source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Recessive mutations in the leptin gene are associated with massive obesity in mice and in some humans, which establishes a genetic basis for obesity.”
§ Leptin at 14 y of age: an ongoing story 1-4 > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Injections or infusions of leptin reduce food intake and body weight of wild-type and ob mice but have no effect on db mice (2)(3)(4)23).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
- Not checked yetcites (2)(3)(4)23)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“to explain the striking stability of weight in living organisms in a stable environment, organisms would need a means for maintaining a constancy of energy stores (5).”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites [5] Bray, 1990, Obesity: historical development of scientific and cultural ideas., Int J Obes
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The first law of thermodynamics applies similarly to inanimate and biological systems.”
§ Leptin at 14 y of age: an ongoing story 1-4 > CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN
What the sources say
- Not checked yetcites [5] Bray, 1990, Obesity: historical development of scientific and cultural ideas., Int J Obes
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“When fat mass decreases, plasma leptin concentrations decrease, which stimulates appetite and suppresses energy expenditure until fat mass is restored.”
§ Leptin at 14 y of age: an ongoing story 1-4 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“In 1994 the ob gene was identified by positional cloning as an '4.5 kb RNA that was expressed exclusively in adipose tissue (1).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
- Not checked yetcites [1] Zhang, 1994, Positional cloning of the mouse obese gene and its human homologue., Nature source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The gene is disrupted in the 2 available alleles of ob; in the original C57/Bl6J ob/ob mutation, a nonsense mutation disrupts protein function, whereas in the second coisogenic ob 2j mutation, a retroviral insertion abrogrates expression of the coding sequence altogether (2,21).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The aforementioned studies using the parabiotic union of mice with lesions of the ventromedial hypothalamus to normal rats further suggested that this receptor was localized in the hypothalamus.”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Leptin is a peptide hormone secreted by adipose tissue and regulates adipose tissue mass and energy balance.”
§ Leptin at 14 y of age: an ongoing story 1-4 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Leptin circulates in the plasma of all mammals tested, including humans and rodents, as an '16-kD protein with a single disulfide bond that is required for bioactivity (2).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
What the sources say
- Not checked yetcites [2] Halaas, 1995, Weight-reducing effects of the plasma protein encoded by the obese gene., Science source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The leptin receptor signals via the Janus kinase-signal transducers and activators of transcription (JAK-Stat) pathway, which depends in part on phosphorylation of tyrosine residues of specific protein substrates, including Stat3 (45).”
§ Leptin at 14 y of age: an ongoing story 1-4 > MOST OBESE PATIENTS ARE LEPTIN RESISTANT
What the sources say
- Not checked yetcites [45] Vaisse, 1996, Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice., Nat Genet source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Importantly, mice with haploinsufficiency for either of these genes are resistant to obesity, remain lean on a high-fat diet, and retain leptin sensitivity (46,47).”
§ Leptin at 14 y of age: an ongoing story 1-4 > MOST OBESE PATIENTS ARE LEPTIN RESISTANT
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Leptin's efficacy was first shown to be variable in rodents in which there was a spectrum of leptin sensitivity among different strains; animals in leptin-deficient states had extreme leptin sensitivity and animals with leptin receptor mutations were the most resistant (23).”
§ Leptin at 14 y of age: an ongoing story 1-4 > MOST OBESE PATIENTS ARE LEPTIN RESISTANT
What the sources say
- Not checked yetcites [23] Halaas, 1997, Physiological response to long-term peripheral and central leptin infusion in lean and obese mice., Proc Natl Acad Sci USA source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Amylin is a peptide hormone secreted from pancreatic b cells that has a number of effects on plasma glucose that are synergistic with insulin.”
§ Leptin at 14 y of age: an ongoing story 1-4 > MOST OBESE PATIENTS ARE LEPTIN RESISTANT
What the sources say
- Not checked yetcites [48] Roth, 2008, Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies., Proc Natl Acad Sci USA source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is now known that the leptin receptor also signals at other central nervous system sites outside the hypothalamus and that its expression at these sites contributes to the broad panoply of leptin's effects (see below).”
§ Leptin at 14 y of age: an ongoing story 1-4 > 973S
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“The clinical significance of these findings was also assessed in humans in which the combination of leptin and amylin resulted in a substantial weight loss of 12.9%, which was significantly greater than that of either agent alone (48).”
§ Leptin at 14 y of age: an ongoing story 1-4 > MOST OBESE PATIENTS ARE LEPTIN RESISTANT
What the sources say
- Not checked yetcites [48] Roth, 2008, Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies., Proc Natl Acad Sci USA source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The data further suggested that there was true synergy between leptin and amylin and that amylin could restore leptin signal transduction in the hypothalamus of DIO (diet-induced obesity) rats.”
§ Leptin at 14 y of age: an ongoing story 1-4 > MOST OBESE PATIENTS ARE LEPTIN RESISTANT
What the sources say
- Not checked yetcites [48] Roth, 2008, Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies., Proc Natl Acad Sci USA source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although leptin has been shown to have potent weight-reducing effects in obese animals with low leptin concentrations, this possibility has not been directly tested in humans (43).”
§ Leptin at 14 y of age: an ongoing story 1-4 > MOST OBESE PATIENTS ARE LEPTIN RESISTANT
What the sources say
- Not checked yetcites [43] Ioffe, 1998, Abnormal regulation of the leptin gene in the pathogenesis of obesity., Proc Natl Acad Sci USA source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Leptin acts by modulating the activity of a set of neural pathways and, in general, activates pathways that inhibit food intake and inhibits pathways that activate food intake.”
§ Leptin at 14 y of age: an ongoing story 1-4 > LEPTIN PROVIDES AN ENTRY POINT FOR STUDYING A COMPLEX HUMAN BEHAVIOR
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A portion of leptin's actions appear to result from inhibition of neuropeptide Y/Agouti gene-related peptide (NPY/AGRP)-expressing neurons in the arcuate nucleus of the hypothalamus.”
§ Leptin at 14 y of age: an ongoing story 1-4 > LEPTIN PROVIDES AN ENTRY POINT FOR STUDYING A COMPLEX HUMAN BEHAVIOR
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Consistent with this, twin studies and other approaches have established a substantial genetic basis for obesity with a heritability of 0.7-0.9, a level exceeded only by height (64).”
§ Leptin at 14 y of age: an ongoing story 1-4 > BIOLOGICAL BASIS FOR OBESITY
What the sources say
- Not checked yetcites [64] Stunkard, 1990, The body-mass index of twins who have been reared apart., N Engl J Med source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The NPY/AGRP neurons act to stimulate appetite.”
§ Leptin at 14 y of age: an ongoing story 1-4 > LEPTIN PROVIDES AN ENTRY POINT FOR STUDYING A COMPLEX HUMAN BEHAVIOR
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Normal individuals typically show this activity only in the starved state and do not show this response after eating.”
§ Leptin at 14 y of age: an ongoing story 1-4 > LEPTIN PROVIDES AN ENTRY POINT FOR STUDYING A COMPLEX HUMAN BEHAVIOR
What the sources say
- Not checked yetcites [52] Farooqi, 2007, Leptin regulates striatal regions and human eating behavior., Science source
- Not checked yetcites [53] Baicy, 2007, Leptin replacement alters brain response to food cues in genetically leptin-deficient adults., Proc Natl Acad Sci USA source
- Not checked yetcites [54] Licinio, 2007, Effects of leptin on intake of specific micro- and macronutrients in a woman with leptin gene deficiency studied off and on leptin at stable body weight., Appetite source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Obese individuals on average earn less money than their no-better-qualified lean counterparts and are promoted less readily (65,66).”
§ Leptin at 14 y of age: an ongoing story 1-4 > BIOLOGICAL BASIS FOR OBESITY
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
The majority of obese subjects are leptin resistant.
“The majority of obese subjects are leptin resistant, which establishes that obesity is the result of hormone resistance.”
The paper relies on this without support.
Leptin treatment results in weight loss in a subset of obese patients and can synergize with other antiobesity agents to reduce weight.
“Leptin treatment results in weight loss in a subset of obese patients and can also synergize with other antiobesity agents to reduce weight.”
The paper relies on this without support.
Diet-induced obesity in animals is a reliable predictor of leptin responses in humans.
“often a reliable predictor of responses in humans”
The paper relies on this without support.
Basic drives typically trump a conscious desire.
“There are innumerable instances in our common experience suggesting that basic drives typically trump a conscious desire.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“However, leptin deficiency is rare in humans, and most obese humans suffer from leptin resistance,, so administration of leptin shows effects in only a small fraction of patients 151.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [151]
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Self-citationMolecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Self-citationEffects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., et al. (1995) · Nature Medicine · doi:10.1038/nm1195-1155 · Cited by 3,725
Self-citationIdentification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.-M., et al. (1998) · Nature · doi:10.1038/32911 · Cited by 2,346
Cited by
Sorted by citations
Lipid Droplets and Cellular Lipid Metabolism
Walther, T. C., & Farese, R. V. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061009-102430 · Cited by 1,701
Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons
Vong, L., Ye, C., Yang, Z., Choi, B. J., Chua, S. C., & Lowell, B. B. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.028 · Cited by 1,237
Adipogenesis: From Stem Cell to Adipocyte
Tang, Q. Q., & Lane, M. D. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052110-115718 · Cited by 897
Treatment of Obesity with Celastrol
Liu, J., Lee, J., Salazar Hernandez, M. A., Mazitschek, R., & Ozcan, U. (2015) · Cell · doi:10.1016/j.cell.2015.05.011 · Cited by 726
Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome
Kahn, C. R., Wang, G., & Lee, K. Y. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129187 · Cited by 686
Metadata
- Authors
- Friedman, J. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Friedman, Jeffrey M
- ORCID
- Friedman, Jeffrey M
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 89
- Issue
- 3
- Pages
- 973S-979S
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC2667654
- OpenAlex
- W1966203604
- Semantic Scholar
- 4a57bde9497d6d58e86fda9cf95e30ecba543b0d
- Cited by
- 272
- References
- 73
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 13 · 2016: 16 · 2015: 24 · 2014: 23 · 2013: 34 · 2012: 37
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Keywords
- leptin, leptin gene, obesity, adipose tissue, energy balance, appetite regulation, energy expenditure, dietary intake, adolescents, leptin receptor mutation
- MeSH terms
- Adipose Tissue, Animals, Body Weight, Cloning, Molecular, Humans, Leptin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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