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Cited by 272Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesPharmacology and Obesity Treatment

Leptin at 14 y of age: an ongoing story

Open access
Friedman, Jeffrey M·2009·The American Journal of Clinical Nutrition
DOI 10.3945/ajcn.2008.26788bPMC PMC2667654
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Abstract

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.

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.

Integrity signals

Registry

Crossref · 10.3945/ajcn.2008.26788b

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 85 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (2,(7)(8)(9)(10)(11)

      Not checked in the free run.

  • Premisecitation

    These mutant mice show an identical phenotype to animals with null mutations of the leptin receptor or leptin itself.

    “These mutant mice show an identical phenotype to animals with null mutations of the leptin receptor or leptin itself (25,26).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Lee, 1996, Abnormal splicing of the leptin receptor indiabetic mice., Nature source

      Not checked in the free run.

    • cites [26] Chen, 1996, Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene indb/db mice., Cell source

      Not checked in the free run.

  • Interpretationreasoning

    Food intake and body weight-or, more precisely, adipose tissue mass-were regulated by an endocrine system.

    “food intake and body weight-or, more precisely, adipose tissue mass-were regulated by an endocrine system.”
    Quote in the paperSubstantial claim
  • Premisecitation

    ObRb was highly enriched in the hypothalamus in precisely those nuclei that alter body weight when lesioned.

    “ObRb was highly enriched in the hypothalamus in precisely those nuclei that alter body weight when lesioned (25,27).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Lee, 1996, Abnormal splicing of the leptin receptor indiabetic mice., Nature source

      Not checked in the free run.

    • cites [27] Fei, 1997, Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues., Proc Natl Acad Sci USA source

      Not checked in the free run.

  • Interpretationreasoning

    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.

    “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.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 21
  • May combine two claims. 28

  • Classified as probably not a substantial claim. May combine two claims.

    Premisereasoning

    When fat mass increases, leptin concentrations increase, which suppresses appetite until weight is lost.

    “When fat mass increases, leptin concentrations increase, which suppresses appetite until weight is lost.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The phenotypes of both mutations are strikingly similar, which suggests that the encoded genes function in the same physiologic pathway.

    “The phenotypes of both mutations are strikingly similar, which suggests that the encoded genes function in the same physiologic pathway.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The leptin receptor was identified biochemically and shown to be a cytokine family receptor that is expressed broadly.

    “The leptin receptor was identifiedbiochemically and shown tobe a cytokine family receptor that is expressed broadly (24).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Tartaglia, 1995, Identification and expression cloning of a leptin receptor, OB-R., Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Leptin concentrations increase with accretion of adipose tissue mass and decrease when adipose mass is lost.

    “Leptin concentrations increase with accretion of adipose tissue mass and decrease when adipose mass is lost (22).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Maffei, 1995, Leptin levels in human and rodent: measurement of plasma leptin andob RNA in obese and weight-reduced subjects., Nat Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure.

    “Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Brobeck, 1946, Mechanism of the development of obesity in animals with hypothalamic lesions., Physiol Rev source

      Not checked in the free run.

    • cites [15] Mayer, 1955, Regulation of energy intake and the body weight: the glucostatic theory and the lipostatic hypothesis., Ann NY Acad Sci source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    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.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Halaas, 1995, Weight-reducing effects of the plasma protein encoded by the obese gene., Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    All these data suggested that there must be a biological system that regulates food intake and maintains homeostatic control of body weight.

    “All these data suggested that there must be a biological system that regulates food intake and maintains homeostatic control of body weight (12).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Adolph, 1947, Urges to eat and drink in rats., Am J Physiol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Results from parabiosis experiments suggested that the ob gene encoded a circulating factor that suppressed food intake and body weight and that the db gene encoded its receptor.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Leptin receptor RNA was alternatively spliced and 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.

    “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).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Lee, 1996, Abnormal splicing of the leptin receptor indiabetic mice., Nature source

      Not checked in the free run.

    • cites [26] Chen, 1996, Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene indb/db mice., Cell source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (1)(2)(3)(4)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Hetherington, 1942, The spontaneous activity and food intake of rats with hypothalamic lesions., Am J Physiol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Recessive mutations in the leptin gene are associated with massive obesity in mice and in some humans, which establishes a genetic basis for obesity.

    “Recessive mutations in the leptin gene are associated with massive obesity in mice and in some humans, which establishes a genetic basis for obesity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Injections or infusions of leptin reduce food intake and body weight of wild-type and ob mice but have no effect on db mice.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (2)(3)(4)23)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Bray, 1990, Obesity: historical development of scientific and cultural ideas., Int J Obes

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The first law of thermodynamics applies similarly to inanimate and biological systems.

    “The first law of thermodynamics applies similarly to inanimate and biological systems.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Bray, 1990, Obesity: historical development of scientific and cultural ideas., Int J Obes

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    When fat mass decreases, plasma leptin concentrations decrease, which stimulates appetite and suppresses energy expenditure until fat mass is restored.

    “When fat mass decreases, plasma leptin concentrations decrease, which stimulates appetite and suppresses energy expenditure until fat mass is restored.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In 1994 the ob gene was identified by positional cloning as a '4.5 kb RNA that was expressed exclusively in adipose tissue.

    “In 1994 the ob gene was identified by positional cloning as an '4.5 kb RNA that was expressed exclusively in adipose tissue (1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Zhang, 1994, Positional cloning of the mouse obese gene and its human homologue., Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Halaas, 1995, Weight-reducing effects of the plasma protein encoded by the obese gene., Science source

      Not checked in the free run.

    • cites [21] Moon, 1997, The molecular basis of the obese mutation in ob2J mice., Genomics source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The receptor was localized in the hypothalamus.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Leptin is a peptide hormone secreted by adipose tissue and regulates adipose tissue mass and energy balance.

    “Leptin is a peptide hormone secreted by adipose tissue and regulates adipose tissue mass and energy balance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Halaas, 1995, Weight-reducing effects of the plasma protein encoded by the obese gene., Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The leptin receptor signals via the JAK-Stat pathway, which depends in part on phosphorylation of tyrosine residues of specific protein substrates, including Stat3.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mice with haploinsufficiency for either SOCS3 or PT1b are resistant to obesity, remain lean on a high-fat diet, and retain leptin sensitivity.

    “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).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [46] Bjørbaek, 1998, Identification of SOC-3 as a potential mediator of central leptin resistance., Mol Cell source

      Not checked in the free run.

    • cites [47] Zabolotny, 2008, Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo., J Biol Chem source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rodents, leptin sensitivity varies among strains: leptin-deficient animals are extremely sensitive, and animals with leptin receptor mutations are most resistant.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Halaas, 1997, Physiological response to long-term peripheral and central leptin infusion in lean and obese mice., Proc Natl Acad Sci USA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Amylin is a peptide hormone secreted from pancreatic beta cells that has effects on plasma glucose synergistic with insulin.

    “Amylin is a peptide hormone secreted from pancreatic b cells that has a number of effects on plasma glucose that are synergistic with insulin.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    The leptin receptor also signals at other central nervous system sites outside the hypothalamus and its expression at these sites contributes to the broad panoply of leptin's effects.

    “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).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In humans, 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.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    There is true synergy between leptin and amylin, and amylin can restore leptin signal transduction in the hypothalamus of diet-induced obesity rats.

    “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.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Leptin has potent weight-reducing effects in obese animals with low leptin concentrations.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Ioffe, 1998, Abnormal regulation of the leptin gene in the pathogenesis of obesity., Proc Natl Acad Sci USA source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Leptin acts by modulating neural pathways, generally activating pathways that inhibit food intake and inhibiting pathways that activate food intake.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    A portion of leptin's actions result from inhibition of neuropeptide Y/Agouti gene-related peptide (NPY/AGRP)-expressing neurons in the arcuate nucleus of the hypothalamus.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Stunkard, 1990, The body-mass index of twins who have been reared apart., N Engl J Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    NPY/AGRP neurons act to stimulate appetite.

    “The NPY/AGRP neurons act to stimulate appetite.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Normal individuals typically show this activity only in the starved state and do not show this response after eating.

    “Normal individuals typically show this activity only in the starved state and do not show this response after eating.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [52] Farooqi, 2007, Leptin regulates striatal regions and human eating behavior., Science source

      Not checked in the free run.

    • cites [53] Baicy, 2007, Leptin replacement alters brain response to food cues in genetically leptin-deficient adults., Proc Natl Acad Sci USA source

      Not checked in the free run.

    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Obese individuals on average earn less money than their no-better-qualified lean counterparts and are promoted less readily.

    “Obese individuals on average earn less money than their no-better-qualified lean counterparts and are promoted less readily (65,66).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] Friedman, 2004, Modern science vs. the stigma of obesity., Nat Med source

      Not checked in the free run.

    • cites [66] Friedman, 2003, A war on obesity, not the obese., Science source

      Not checked in the free run.

37 of 37

  • 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.”
4 of 4

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?

  • 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.

    “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]

Cites

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Related

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)
DOI
10.3945/ajcn.2008.26788b
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
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Pharmacology › 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

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