Resistin

Resistin was discovered in 2001 and identified as a hormone produced by adipose tissue, with a role in promoting insulin resistance.{{cite journal | vauthors = Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA | title = The hormone resistin links obesity to diabetes | journal = Nature | volume = 409 | issue = 6818 | pages = 307–312 | date = January 2001 | pmid = 11201732 | doi = 10.1038/35053000 | s2cid = 4358808 }} Elevated resistin levels were linked to insulin resistance and were shown to increase with obesity, supporting its role in metabolic dysfunction.{{cite journal | vauthors = Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, Zhu Q, Considine RV | title = Serum resistin (FIZZ3) protein is increased in obese humans | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 11 | pages = 5452–5455 | date = November 2003 | pmid = 14602788 | doi = 10.1210/jc.2002-021808 | doi-access = free }}{{cite journal | vauthors = Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N | title = Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? | journal = Diabetes | volume = 51 | issue = 10 | pages = 2951–2958 | date = October 2002 | pmid = 12351432 | doi = 10.2337/diabetes.51.10.2951 | doi-access = free }}{{cite journal | vauthors = Levy JR, Davenport B, Clore JN, Stevens W | title = Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344 rats | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 282 | issue = 3 | pages = E626–E633 | date = March 2002 | pmid = 11832366 | doi = 10.1152/ajpendo.00346.2001 | s2cid = 25303054 }}{{cite journal | vauthors = McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S | title = Resistin, central obesity, and type 2 diabetes | journal = Lancet | location = London, England | volume = 359 | issue = 9300 | pages = 46–47 | date = January 2002 | pmid = 11809189 | doi = 10.1016/S0140-6736(02)07281-1 | s2cid = 21927880 }}

Subsequent studies highlighted resistin’s involvement in inflammatory processes and energy homeostasis, indicating a broader physiological role beyond insulin resistance.{{cite journal | vauthors = Adeghate E | title = An update on the biology and physiology of resistin | journal = Cellular and Molecular Life Sciences | volume = 61 | issue = 19–20 | pages = 2485–2496 | date = October 2004 | pmid = 15526156 | pmc = 11924563 | doi = 10.1007/s00018-004-4083-2 | s2cid = 22832421 }}{{cite journal | vauthors = Stumvoll M, Häring H | title = Resistin and adiponectin--of mice and men | journal = Obesity Research | volume = 10 | issue = 11 | pages = 1197–1199 | date = November 2002 | pmid = 12429885 | doi = 10.1038/oby.2002.162 }}{{cite journal | vauthors = Vendrell J, Broch M, Vilarrasa N, Molina A, Gómez JM, Gutiérrez C, Simón I, Soler J, Richart C | title = Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity | journal = Obesity Research | volume = 12 | issue = 6 | pages = 962–971 | date = June 2004 | pmid = 15229336 | doi = 10.1038/oby.2004.118 | doi-access = free }}

Recent reviews have synthesized these findings, supporting resistin’s proposed role in mediating the link between obesity and insulin resistance, as well as its potential contributions to inflammation and metabolic diseases.{{Cite journal | vauthors = Vidal-Puig A, O'Rahilly S | title = Resistin: a new link between obesity and insulin resistance? | journal = Clinical Endocrinology | volume = 55 | issue = 4 | pages = 437–438 | date = 2001 | pmid = 11678824 | doi = 10.1046/j.1365-2265.2001.01377.x | issn = 0300-0664 | s2cid = 6087337 }}{{Cite journal | vauthors = Lazar MA | title = Resistin- and Obesity-associated metabolic diseases | journal = Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme | volume = 39 | issue = 10 | pages = 710–716 | date = 2007 | pmid = 17952831 | doi = 10.1055/s-2007-985897 | issn = 0018-5043 | doi-access = free }}

{{Infobox protein family

| Symbol = Resistin

| Name = Resistin

| image =

| width =

| caption =

| Pfam= PF06954

| InterPro= IPR009714

| SMART=

| Prosite =

| SCOP = 1rgx

| TCDB =

| OPM family= 384

| OPM protein= 1rgx

| PDB=

}}

Resistin is a cysteine-rich, secreted peptide hormone characterized by a unique multimeric structure. Each resistin monomer consists of a C-terminal, disulfide-rich beta-sandwich "head" domain and an N-terminal alpha-helical "tail" segment.{{cite journal | vauthors = Li Y, Yang Q, Cai D, Guo H, Fang J, Cui H, Gou L, Deng J, Wang Z, Zuo Z | title = Resistin, a Novel Host Defense Peptide of Innate Immunity | journal = Frontiers in Immunology | volume = 12 | pages = 699807 | date = 2021 | pmid = 34220862 | pmc = 8253364 | doi = 10.3389/fimmu.2021.699807 | doi-access = free }}{{cite journal | vauthors = Patel SD, Rajala MW, Rossetti L, Scherer PE, Shapiro L | title = Disulfide-dependent multimeric assembly of resistin family hormones | journal = Science | location = New York, N.Y. | volume = 304 | issue = 5674 | pages = 1154–1158 | date = May 2004 | pmid = 15155948 | doi = 10.1126/science.1093466 | bibcode = 2004Sci...304.1154P }} The head domain adopts a six-stranded jelly-roll topology, forming two three-stranded antiparallel beta-sheets, while the tail segments associate to create three-stranded coiled coils. These monomers assemble into trimers, and further interchain disulfide linkages mediate the formation of tail-to-tail hexamers, resulting in a multimeric assembly stabilized by disulfide bonds. The C-terminal head domain is notable for its positive electrostatic surface and exposed hydrophobic residues, which may contribute to the protein’s biological activity, including its antimicrobial properties. In circulation, resistin exists in multiple assembly states, including high-molecular-mass hexamers and lower-molecular-mass trimers, with the oligomeric form in humans showing greater proinflammatory activity. This structural organization is highly conserved within the resistin-like molecule (RELM) family and is thought to underpin resistin’s diverse physiological roles.

Resistin is a multifunctional, cysteine-rich peptide hormone that plays critical roles in metabolic regulation, inflammation, and innate immunity. In humans, resistin is primarily expressed by immune cells such as monocytes and macrophages, where it acts as a pro-inflammatory cytokine by stimulating the production of cytokines including IL-6, IL-1β, and TNF-α through activation of signaling pathways involving the TLR4 and CAP1 receptors.{{cite journal | vauthors = Lee S, Lee HC, Kwon YW, Lee SE, Cho Y, Kim J, Lee S, Kim JY, Lee J, Yang HM, Mook-Jung I, Nam KY, Chung J, Lazar MA, Kim HS | title = Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes | journal = Cell Metabolism | volume = 19 | issue = 3 | pages = 484–97 | date = March 2014 | pmid = 24606903 | pmc = 3969988 | doi = 10.1016/j.cmet.2014.01.013 | url = }} Beyond its pro-inflammatory effects, resistin also demonstrates direct antimicrobial activity by damaging bacterial membranes, and it modulates immune responses by recruiting and activating immune cells, promoting chemokine production, and enhancing the formation of neutrophil extracellular traps (NETs). Notably, resistin exhibits bidirectional immunomodulatory properties: while it can amplify inflammation in response to certain stimuli, it can also attenuate excessive inflammatory responses triggered by bacterial products such as lipopolysaccharide (LPS), potentially by competing for TLR4 binding or directly neutralizing LPS. This dual functionality positions resistin as an important regulator of host defense and inflammatory balance in both health and disease.

Inflammation is the first innate immune response to infection or irritation resulting from leukocyte (neutrophils, mast cells, etc.) accumulation and their secretion of inflammatory, biogenic chemicals such as histamine, prostaglandin, and pro-inflammatory cytokines. As cited, it has recently been discovered that resistin also participates in the inflammatory response.{{cite journal | vauthors = Holcomb IN, Kabakoff RC, Chan B, Baker TW, Gurney A, Henzel W, Nelson C, Lowman HB, Wright BD, Skelton NJ, Frantz GD, Tumas DB, Peale Jr FV, Shelton DL, Hébert CC | title = FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family | journal = The EMBO Journal | volume = 19 | issue = 15 | pages = 4046–4055 | date = August 2000 | pmid = 10921885 | pmc = 306596 | doi = 10.1093/emboj/19.15.4046 }}{{cite journal | vauthors = Kusminski CM, da Silva NF, Creely SJ, Fisher FM, Harte AL, Baker AR, Kumar S, McTernan PG | title = The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 1 | pages = 270–276 | date = January 2007 | pmid = 17062773 | doi = 10.1210/jc.2006-1151 | doi-access = free }}{{cite journal | vauthors = Malyszko J, Malyszko JS, Pawlak K, Mysliwiec M | title = Resistin, a new adipokine, is related to inflammation and renal function in kidney allograft recipients | journal = Transplantation Proceedings | volume = 38 | issue = 10 | pages = 3434–3436 | date = December 2006 | pmid = 17175295 | doi = 10.1016/j.transproceed.2006.10.140 }}{{cite journal | vauthors = Nagaev I, Bokarewa M, Tarkowski A, Smith U | veditors = Valcarcel J | title = Human Resistin Is a Systemic Immune-Derived Proinflammatory Cytokine Targeting both Leukocytes and Adipocytes | journal = PLOS ONE | volume = 1 | issue = 1 | pages = e31 | date = Dec 2006 | pmid = 17183659 | pmc = 1762367 | doi = 10.1371/journal.pone.0000031 | bibcode = 2006PLoSO...1...31N | doi-access = free }}

In further support of its inflammatory profile, resistin has been shown to increase transcriptional events, leading to an increased expression of several pro-inflammatory cytokines including (but not limited to) interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), and tumor necrosis factor-α (TNF-α) in an NF-κB-mediated (nuclear factor kappa-light-chain-enhancer of activated B cells-mediated) fashion.{{cite journal | vauthors = Milan G, Granzotto M, Scarda A, Calcagno A, Pagano C, Federspil G, Vettor R | title = Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss | journal = Obesity Research | volume = 10 | issue = 11 | pages = 1095–1103 | date = November 2002 | pmid = 12429872 | doi = 10.1038/oby.2002.149 | doi-access = free }}{{cite journal | vauthors = Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ | title = Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway | journal = Biochemical and Biophysical Research Communications | volume = 334 | issue = 4 | pages = 1092–1101 | date = September 2005 | pmid = 16039994 | doi = 10.1016/j.bbrc.2005.06.202 | s2cid = 29273978 }} It has also been demonstrated that resistin upregulates intercellular adhesion molecule-1 (ICAM1) vascular cell-adhesion molecule-1 (VCAM1) and chemokine (C-C motif) ligand 2 (CCL2), all of which are occupied in chemotactic pathways involved in leukocyte recruitment to sites of infection.{{cite journal | vauthors = Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, Mickle DA | title = Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction | journal = Circulation | volume = 108 | issue = 6 | pages = 736–740 | date = August 2003 | pmid = 12874180 | doi = 10.1161/01.CIR.0000084503.91330.49 | doi-access = free }} Resistin itself can be upregulated by interleukins and also by microbial antigens such as lipopolysaccharide,{{cite journal | vauthors = Lu SC, Shieh WY, Chen CY, Hsu SC, Chen HL | title = Lipopolysaccharide increases resistin gene expression in vivo and in vitro | journal = FEBS Letters | volume = 530 | issue = 1–3 | pages = 158–162 | date = October 2002 | pmid = 12387885 | doi = 10.1016/S0014-5793(02)03450-6 | s2cid = 45491974 }} which are recognized by leukocytes. Taken together, because resistin is reputed to contribute to insulin resistance, results such as those mentioned suggest that resistin may be a link in the well-known association between inflammation and insulin resistance.{{cite journal | vauthors = Wellen KE, Hotamisligil GS | title = Inflammation, stress, and diabetes | journal = The Journal of Clinical Investigation | volume = 115 | issue = 5 | pages = 1111–1119 | date = May 2005 | pmid = 15864338 | pmc = 1087185 | doi = 10.1172/JCI25102 }}

In accordance, it is expected that, if resistin does serve as a link between obesity and T2DM while at the same time contributing to the inflammatory response, then proportional increases in chronic inflammation in association with obesity and insulin resistance should be observed. Recent data has shown that this is possible by demonstrating positive correlations between obesity, insulin resistance, and chronic inflammation,{{cite journal | vauthors = Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME | title = Adiponectin differentially regulates cytokines in porcine macrophages | journal = Biochemical and Biophysical Research Communications | volume = 316 | issue = 3 | pages = 924–929 | date = April 2004 | pmid = 15033490 | doi = 10.1016/j.bbrc.2004.02.130 }}{{cite journal | vauthors = Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y | title = Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages | journal = Blood | volume = 96 | issue = 5 | pages = 1723–1732 | date = September 2000 | pmid = 10961870 | doi = 10.1182/blood.V96.5.1723 | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=10961870 | url-access = subscription }} which is believed to be directed in part by resistin signaling. This idea has recently been challenged by a study showing that increased levels of resistin in people with chronic kidney disease are associated with lowered renal function and inflammation, but not with insulin resistance.{{cite journal | vauthors = Axelsson J, Bergsten A, Qureshi AR, Heimbürger O, Bárány P, Lönnqvist F, Lindholm B, Nordfors L, Alvestrand A, Stenvinkel P | title = Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance | journal = Kidney International | volume = 69 | issue = 3 | pages = 596–604 | date = February 2006 | pmid = 16395259 | doi = 10.1038/sj.ki.5000089 | doi-access = free }} Notwithstanding, regarding resistin and the inflammatory response, it can be concluded that resistin does bear features of a pro-inflammatory cytokine, and could act as a key node in inflammatory diseases with or without associated insulin resistance.

This adipokine is associated with markers of inflammation in seminal plasma and the concentrations of seminal resistin correlate positively with those of proinflammatory mediators such as interleukin-6 (IL-6), elastase and tumor necrosis factor-α (TNF-α). During inflammation, the concentrations of cytokines and ROS increase, and this may have a deleterious effect on the male reproductive function.{{cite journal | vauthors = Elfassy Y, Bastard JP, McAvoy C, Fellahi S, Dupont J, Levy R | title = Adipokines in Semen: Physiopathology and Effects on Spermatozoas | journal = International Journal of Endocrinology | volume = 2018 | pages = 3906490 | date = 2018 | pmid = 29971101 | pmc = 6008818 | doi = 10.1155/2018/3906490 | doi-access = free }} One study showed that there was a negative correlation between the concentrations of seminal resistin and spermatic motility and vitality. (The seminal concentrations of resistin were significantly higher in cases of leukocyte spermia or if the patients were smokers.){{cite journal | vauthors = Moretti E, Micheli L, Noto D, Fiaschi AI, Menchiari A, Cerretani D | title = Resistin in Human Seminal Plasma: Relationship with Lipid Peroxidation, CAT Activity, GSH/GSSG Ratio, and Semen Parameters | journal = Oxidative Medicine and Cellular Longevity | volume = 2019 | pages = 2192093 | date = 2019 | pmid = 31772701 | pmc = 6854241 | doi = 10.1155/2019/2192093 | doi-access = free }}

Much of what is hypothesized about a resistin role in energy metabolism and T2DM can be derived from studies showing strong correlations between resistin and obesity. The premise being that serum resistin levels increase with increased adiposity.{{cite journal | vauthors = Asensio C, Cettour-Rose P, Theander-Carrillo C, Rohner-Jeanrenaud F, Muzzin P | title = Changes in glycemia by leptin administration or high- fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis | journal = Endocrinology | volume = 145 | issue = 5 | pages = 2206–2213 | date = May 2004 | pmid = 14962997 | doi = 10.1210/en.2003-1679 | doi-access = free }}{{cite journal | vauthors = Lee JH, Bullen JW, Stoyneva VL, Mantzoros CS | title = Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 288 | issue = 3 | pages = E625–E632 | date = March 2005 | pmid = 15522996 | doi = 10.1152/ajpendo.00184.2004 | s2cid = 20609673 }} Conversely, serum resistin levels to decline with decreased adiposity following medical treatment.{{cite journal | vauthors = Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif W, Barnett AH, Kumar S | title = Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines | journal = Metabolism: Clinical and Experimental | volume = 53 | issue = 4 | pages = 430–434 | date = April 2004 | pmid = 15045687 | doi = 10.1016/j.metabol.2003.11.022 }} Specifically, central obesity (waistline adipose tissue) is the region of adipose tissue that contributes most to rising levels of serum resistin.{{cite journal | vauthors = McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S | title = Increased resistin gene and protein expression in human abdominal adipose tissue | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 87 | issue = 5 | pages = 2407 | date = May 2002 | pmid = 11994397 | doi = 10.1210/jcem.87.5.8627 | doi-access = free }} This is significant, considering the link between central obesity and insulin resistance, two marked peculiarities of T2DM.{{cite journal | vauthors = Duman BS, Turkoglu C, Gunay D, Cagatay P, Demiroglu C, Buyukdevrim AS | title = The interrelationship between insulin secretion and action in type 2 diabetes mellitus with different degrees of obesity: evidence supporting central obesity | journal = Diabetes, Nutrition & Metabolism | volume = 16 | issue = 4 | pages = 243–250 | date = August 2003 | pmid = 14768774 }}

Although resistin levels increase with obesity, it is questioned whether this increase is responsible for the insulin resistance associated with increased adiposity.{{Citation needed|date=August 2012}} Several reports have shown a positive correlation between resistin levels and insulin resistance.{{cite journal | vauthors = Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS | title = A central role for JNK in obesity and insulin resistance | journal = Nature | volume = 420 | issue = 6913 | pages = 333–336 | date = November 2002 | pmid = 12447443 | doi = 10.1038/nature01137 | bibcode = 2002Natur.420..333H | url = http://www.hsph.harvard.edu/GSH-LAB/tnf-ins.html | s2cid = 1659156 | url-access = subscription }}{{cite journal | vauthors = Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB, Sinha MK, Gingerich RL, Scherer PE, Ahima RS | title = Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting | journal = Diabetes | volume = 53 | issue = 7 | pages = 1671–1679 | date = July 2004 | pmid = 15220189 | doi = 10.2337/diabetes.53.7.1671 | doi-access = free }}{{cite journal | vauthors = Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ | title = Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance | journal = European Journal of Endocrinology | volume = 149 | issue = 4 | pages = 331–335 | date = October 2003 | pmid = 14514348 | doi = 10.1530/eje.0.1490331 | doi-access = free }}{{cite journal | vauthors = Smith SR, Bai F, Charbonneau C, Janderová L, Argyropoulos G | title = A promoter genotype and oxidative stress potentially link resistin to human insulin resistance | journal = Diabetes | volume = 52 | issue = 7 | pages = 1611–1618 | date = July 2003 | pmid = 12829623 | doi = 10.2337/diabetes.52.7.1611 | doi-access = free }} This is supported by reports of correlation between resistin levels and subjects with T2DM.{{cite journal | vauthors = Fujinami A, Obayashi H, Ohta K, Ichimura T, Nishimura M, Matsui H, Kawahara Y, Yamazaki M, Ogata M, Hasegawa G, Nakamura N, Yoshikawa T, Nakano K, Ohta M | title = Enzyme-linked immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 339 | issue = 1–2 | pages = 57–63 | date = January 2004 | pmid = 14687894 | doi = 10.1016/j.cccn.2003.09.009 }}{{cite journal | vauthors = McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S | title = Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 12 | pages = 6098–6106 | date = December 2003 | pmid = 14671216 | doi = 10.1210/jc.2003-030898 | doi-access = free }} If resistin contributes to the pathogenesis of insulin resistance in T2DM, then designing drugs to promote decreased serum resistin in T2DM subjects may deliver therapeutic benefits.{{cite journal | vauthors = Tjokroprawiro A | title = New approach in the treatment of T2DM and metabolic syndrome (focus on a novel insulin sensitizer) | journal = Acta Medica Indonesiana | volume = 38 | issue = 3 | pages = 160–166 | year = 2006 | pmid = 17119268 }}

Resistin can increase levels of circulating low-density lipoprotein (LDL) and accelerates LDL accumulation in arteries, increasing risk of heart disease has an adverse impact on the efficacy of statins, the primary drug used to reduce cholesterol in fighting of cardiovascular disease.{{Cite web | title = Canadian scientists discover cause of high cholesterol | date = October 28, 2012 | url = https://www.sciencecodex.com/canadian_scientists_discover_cause_of_high_cholesterol-101029 | website = Science Codex }} In the liver, resistin increases LDL production and degrades LDL receptors, impairing the ability to process LDL.

The amount of evidence supporting the resistin link theory between obesity and T2DM is vast.{{Citation needed|date=August 2012}} Nevertheless, this theory lacks support from the entire scientific community, as a number of studies present evidence against it.{{cite journal | vauthors = Fain JN, Cheema PS, Bahouth SW, Lloyd Hiler M | title = Resistin release by human adipose tissue explants in primary culture | journal = Biochemical and Biophysical Research Communications | volume = 300 | issue = 3 | pages = 674–678 | date = January 2003 | pmid = 12507502 | doi = 10.1016/S0006-291X(02)02864-4 }}{{cite journal | vauthors = Lee JH, Chan JL, Yiannakouris N, Kontogianni M, Estrada E, Seip R, Orlova C, Mantzoros CS | title = Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 10 | pages = 4848–4856 | date = October 2003 | pmid = 14557464 | doi = 10.1210/jc.2003-030519 | doi-access = free }}{{cite journal | vauthors = Nagaev I, Smith U | title = Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle | journal = Biochemical and Biophysical Research Communications | volume = 285 | issue = 2 | pages = 561–564 | date = July 2001 | pmid = 11444881 | doi = 10.1006/bbrc.2001.5173 }} Such studies have found significantly decreased serum concentrations of resistin with increased adiposity,{{cite journal | vauthors = Heilbronn LK, Rood J, Janderova L, Albu JB, Kelley DE, Ravussin E, Smith SR | title = Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 89 | issue = 4 | pages = 1844–1848 | date = April 2004 | pmid = 15070954 | doi = 10.1210/jc.2003-031410 | doi-access = free }}{{cite journal | vauthors = Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O'Rahilly S | title = Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans | journal = Diabetes | volume = 50 | issue = 10 | pages = 2199–2202 | date = October 2001 | pmid = 11574398 | doi = 10.2337/diabetes.50.10.2199 | doi-access = free }}{{cite journal | vauthors = Way JM, Görgün CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, ((Oliver WR Jr)), Willson TM, Kliewer SA, Hotamisligil GS | title = Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists | journal = Journal of Biological Chemistry | volume = 276 | issue = 28 | pages = 25651–25653 | date = July 2001 | pmid = 11373275 | doi = 10.1074/jbc.C100189200 | doi-access = free }} suggesting not only that resistin is downregulated in obese subjects, but also that decreased resistin levels may contribute to the links between obesity and T2DM. Data contradicting the idea that weight loss coincides with decreased serum resistin concentrations have also been presented; such studies instead report that weight loss is associated with marked increases in serum resistin. The idea that resistin links obesity to T2DM is under scrutiny, reports have been made of ubiquitous resistin expression in many tissues, rather than only those characteristic of obesity, such as adipocytes {{Citation needed|date=August 2012}}.

Although nearly as many scientists oppose the theory as those who support it {{Citation needed|date=August 2012}}, there is sufficient evidence to support the idea that resistin does have some incompletely defined role in energy homeostasis, while also demonstrating properties that help to incite inflammatory responses to sites of infection.

{{Reflist|2}}

• {{MeshName|Resistin}}

{{Hormones}}

Category:Tissues (biology)

Category:Endocrinology

Category:Obesity