ライフサイエンスコーパス: leptin

1 ] and levels of C-reactive protein [CRP] and leptin).

2 echanisms may account for this regulation by leptin.

3 ly understand the antidiabetic mechanisms of leptin.

4 as enhanced by the obesity-related adipokine leptin.

5 rs in hypothalamus at lower dose than native leptin.

6 otein 28 (RBM28) was in closest proximity to leptin.

7 iological concentrations of T3 , insulin and leptin.

8 regulated synthesis of transcripts encoding leptin.

9 (all P < 0.05), but not with adiponectin and leptin.

10 at diet-induced obesity) blunt the effect of leptin.

11 ed circulating concentrations of insulin and leptin.

12 ral except for an association with decreased leptin.

13 trimester with post-delivery maternal serum leptin.

14 l of metabolic and cardiovascular actions by leptin.

15 ne receptor phosphorylation, were reduced by leptin.

16 f triglycerides, free fatty acids (FFA), and leptin?

17 weeks after surgery, animals received either leptin (0.36 mg kg(-1) day(-1) ) or vehicle via osmotic

18 ) and SHBG (19%) and lower concentrations of leptin (18%) (all P-trend </= 0.02).

19 in (SHBG) (21%), and lower concentrations of leptin (28%), triglycerides (19%), and C-peptide (4%) (a

20 After control measurements, leptin (4 mug/kg/min) or saline vehicle was infused for

21 ons projecting to the VTA were suppressed by leptin, a peptide hormone derived from adipocytes that s

22 ase manifestations and the administration of leptin accelerated development of autoantibodies and ren

23 Central leptin action is sufficient to restore euglycemia in ins

24 ng neurotransmitter release, is required for leptin action on euglycemia restoration and that hypergl

25 Thus, decreased leptin action on PAG LepRb neurons augments the autonomi

26 proopiomelanocortin (POMC) neurons disrupts leptin action, reduces melanocortin content in the parav

27 This study tested whether leptin actions on AgRP neurons are required and sufficie

28 We find that leptin activates mechanisms that contribute to cardiac d

29 We assessed leptin, adiponectin, and homeostatic model assessment of

30 asma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring.

31 ls of insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, and cytokines.

32 we found that primate pituitaries expressed leptin/adiponectin/resistin.

33 new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone bind

34 Leptin, an adipocyte-derived hormone, acts on neurons lo

35 ior can be restored by substitution with the leptin analog metreleptin.

36 The change in maternal lipid, leptin and adiponectin concentrations during pregnancy a

37 Serum leptin and adiponectin levels were measured.

38 eter </=2.5 microm) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear

39 evaluate the association of maternal lipids, leptin and adiponectin throughout pregnancy with large-f

40 irth weight and cord blood concentrations of leptin and adiponectin using data on 1,705 mother-infant

41 and indicators of metabolic function (i.e., leptin and adiponectin) has received limited attention.

42 organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate

43 Blood levels of leptin and adiposity indexes (body mass index and waist

44 cretion in explants increased in response to leptin and decreased with leptin receptor signaling inhi

45 Sexual dimorphism in leptin and fat stores have been observed in humans and r

46 humans and rodents with females having more leptin and greater levels of subcutaneous fat than males

47 ents were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolle

48 reased the abundance of transcripts encoding leptin and increased secreted leptin to 230% of the cont

49 Significantly increased serum leptin and insulin concentrations and impaired insulin t

50 halamus plays a crucial role in mediation of leptin and insulin function.

51 Lactalbumin and lactoferrin decreased plasma leptin and insulin, and lactalbumin increased peptide YY

52 rmalized circulating levels of the cytokines leptin and interleukin 1beta and decreased peritoneal pr

53 We asked if leptin and its cognate receptor were present in normal a

54 pocampus to a greater extent than the native leptin and LepNPEG5K and activated leptin receptors in h

55 athers exhibited increased adiposity, plasma leptin and luteinising hormone to testosterone ratio.

56 lation (R = - 0.7) between the expression of leptin and of RBM28 across tissues that expressed at lea

57 Leptin and resistin stimulated GH-release, a response th

58 yses indicated that levels of the adipokines leptin and resistin, the inflammatory marker myeloperoxi

59 s the second trimester with fetal cord blood leptin and stronger association beginning as early as th

60 bition between the reward-related effects of leptin and the reward-related effects of cocaine in rats

61 ns but remained significant for 1) DASH with leptin and triglycerides and 2) the aMED with triglyceri

62 with endocrine factors such as adiponectin, leptin, and C-reactive protein which may be associated w

63 ession and HOMA-IR, glucose, insulin, HbA1c, leptin, and high-sensitivity C-reactive protein levels f

64 Body fat, leptin, and insulin were increased in male, but not in f

65 Treating leptin- and corticosterone-infused rats with an adipose

66 Recombinant virus (rAAV) leptin antagonism in the VTA decreased wheel running in

67 ng that are differentially influenced by VTA leptin antagonism.

68 findings reveal that the trophic actions of leptin are contingent upon timing and duration of leptin

69 ther the chronic BP and metabolic actions of leptin are differentially modulated by changes in ambien

70 nstrate that the chronic anorexic effects of leptin are enhanced at TNZ, while its effects on insulin

71 expression and secretion of IL-6, MCP-1 and leptin, as well as suppressed the overexpression of PAI-

72 ree key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine o

73 uring starvation and have been implicated in leptin-associated infertility.

74 re sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for panc

75 hose effects were independent of feeding and leptin but were related to increased thermogenic activat

76 as stronger for increasing adiposity levels (leptin by body mass index interaction, p < .02), strengt

77 activation of NMDARs mimicked the effect of leptin, causing Ca(2+) influx, AMPK activation, and incr

78 lar cell adhesion molecule-1, 8-isoprostane, leptin, circulating AGEs and receptor for AGEs were redu

79 Reductions in circulating leptin concentrations reflect a negative energy balance,

80 Circulating leptin concentrations were associated with global longit

81 hyperplasia, and elevated plasma insulin and leptin concentrations.

82 ugate with the native leptin, the N-terminal leptin conjugate with poly(ethylene glycol) (LepNPEG5K),

83 Leptin contributes to the control of resting metabolic r

84 -density lipoprotein particle concentration, leptin, d-dimer, homoarginine, and N-terminal pro B-type

85 3.1 was administered daily by oral gavage to leptin (db/db) mice for 5 weeks starting from 3 weeks of

86 and tan, brachyury (BTBR) mouse strain with leptin deficiency (Lep(ob)) has emerged as one of the be

87 We also showed that Leptin deficiency (ob/ob) increased lipogenesis and prol

88 ith a paucity of subcutaneous adipocytes and leptin deficiency.

89 induced by both high-fat diet treatment and leptin deficiency.

90 ese projections are significantly reduced in leptin deficient (Lep(ob/ob) ) mice and this phenotype i

91 that expression of CTRP6 is up-regulated in leptin-deficient mice and, conversely, down-regulated by

92 improves hepatic inflammation and damage in leptin-deficient ob/ob mice and in choline-deficient mic

93 erleukin-10 (IL-10) were further examined in leptin-deficient ob/ob mice.

94 The regulatory effects of leptin depend on intact leptin receptor signaling.

95 and sex specificity, and that modulation of leptin-dependent circuit formation by each of these fact

96 ucose intolerance is largely a result of its leptin-dependent effects on adiposity and, to a lesser e

97 However, leptin-dependent effects on augmenting chemokine express

98 Peripheral resistance to leptin due to its impaired brain delivery prevents thera

99 h, we treated Lep(ob/ob) mice with exogenous leptin during a variety of discrete time periods, and me

100 Leptin dysregulation (resistance) may represent an under

101 However, evidence for leptin dysregulation in major depressive disorder (MDD)

102 owever, the mechanism or mechanisms by which leptin exerts glycemic control are unclear.

103 Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline.

104 The duration of leptin exposure appears to be important, with 9- or 11-d

105 n are contingent upon timing and duration of leptin exposure, display both target and sex specificity

106 balance and glucose homeostasis by promoting leptin expression and secretion in WAT.

107 r massive adipose overgrowth with suppressed leptin expression in four further patients with bialleli

108 ss adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therap

109 h collagenous structure) and mannose-binding leptin expression.

110 6-type cytokines may increase the release of leptin from adipocytes and by those means induce glucago

111 , IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-alpha.

112 Misidentification of the chicken leptin gene has hampered research of leptin signaling in

113 Recently, the genuine leptin gene with a GC-rich ( 70%) repetitive-sequence co

114 ed to map the genome location of the chicken leptin gene.

115 eceive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implica

116 d impaired glucose tolerance and circulating leptin, GLP-1, and insulin levels were reduced.

117 receptors in hippocampal neurons to reduce (leptin, glucagon-like peptide-1) or increase (ghrelin) f

118 ed cells increasingly secreting adiponectin, leptin, glycerol and total triglycerides.

119 The leptin > melanocortin > SIM1 pathway is dysregulated in

120 ious on cardiac function in control animals, leptin had a cardioprotective effect following TAC, norm

121 was deleterious on cardiac function in sham, leptin had a cardioprotective effect following TAC.

122 Leptin has been shown to effectively restore euglycemia

123 In contrast, the hormone leptin has no acute effect on dynamics of these circuits

124 Maternal HFD also increased plasma leptin, IL-6, and MCP-1 in WT and increased arcuate expr

125 rast, the chronic glucose-lowering effect of leptin in a STZ-induced mouse model of poorly controlled

126 ion and expression of PAI-1, IL-6, MCP-1 and leptin in mature 3T3-L1 adipocytes under baseline condit

127 e inter-individual variation of BMI, WC, and leptin in our population.

128 d brain delivery prevents therapeutic use of leptin in overweight and moderately obese patients.

129 The role of leptin in the development of SLE was confirmed in the Ne

130 the chemoreflex may depend on the action of leptin in the hindbrain areas involved in the respirator

131 stingly, the synaptic regulatory function of leptin in the LHA-to-VTA neuronal pathway is highly sens

132 sleep duration and quality, adiponectin and leptin, in 2962 participants (1116 men and 1810 women) f

133 Leptin increased basal WBCs, decreased basal and AMD3100

134 These findings demonstrate a leptin-independent body weight homeostat ("gravitostat")

135 The hormone leptin indirectly communicates metabolic information to

136 Leptin induced a bimodal response whereby beta cell prol

137 Leptin-induced decreases in lipolysis, HGP, and ketogene

138 ized leptin's anorectic effect, and enhanced leptin-induced STAT3 activation in the hypothalamus.

139 At 15 degrees C, leptin infusion did not alter food intake but increased

140 Leptin infusion reduced rates of lipolysis, hepatic gluc

141 These beneficial effects of leptin involve restoration of action potential duration

142 Taken together, these data suggest that leptin is a functionally active product of the parathyro

143 Leptin is an adipocyte-derived hormone involved in energ

144 Leptin is an adipocyte-secreted hormone that is delivere

145 Leptin is an adipokine involved in regulating energy bal

146 Leptin is an adipokine produced by fat cells that regula

147 Leptin is an adipose tissue hormone that functions as an

148 ctive, suggesting that the trophic action of leptin is limited to a developmental critical period.

149 Leptin is the primary adipostatic factor in mammals.

150 KEY POINTS: Leptin, is a 16 kDa pleiotropic peptide not only primari

151 ABSTRACT: Leptin, is a 16 kDa pleiotropic peptide not only primary

152 onal ortholog of the primary human adipokine leptin, is released from Drosophila fat cells.

153 sed levels of the pro-inflammatory adipokine leptin, leading to greater production of IL-6 in OA pati

154 rain responds as if there were low levels of leptin, leading to increased appetite and suppressed fer

155 study investigates the role of the adipokine leptin (LEP) in the regulation of human APC biological f

156 trate that dihydrotestosterone (DHT) reduced Leptin (Lep) transcript abundance and cytosolic and secr

157 Leptin, leptin receptor (long isoform), and PTH mRNA tra

158 d a nonsignificant positive association with leptin levels [MD=0.37 (95% CI: -0.14, 0.87)] and a sign

159 eight, these mice have decreased circulating leptin levels compared to their wild-type littermates.

160 use model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and

161 Leptin levels fall during starvation and elicit adaptive

162 ishment of pressure overload, an increase in leptin levels has protective cardiac effects with respec

163 ines was consistently associated with higher leptin levels in both cord blood and post-delivery mater

164 between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z

165 loci robustly associated (P<5 x 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO.

166 In Hdc(-/-) HFD mice, serum leptin levels increased, whereas biliary Ob-R expression

167 Histamine and leptin levels were measured by enzyme immunoassay.

168 lso seen in patients with constitutively low leptin levels, such as occur in lipodystrophy.

169 causal gene in the SLC32A1 locus influencing leptin levels.

170 expectancy of cocaine each depresses plasma leptin levels.

171 ark of obesity is an increase in circulating leptin levels; despite this, the brain responds as if th

172 = 2.1, P = 2.8 x 10(-7)), and inhibition of leptin-like signaling (z = -2.6, P = 3.9 x 10(-5)).

173 The results indicate that leptin loses its neurotrophic potential at or near postn

174 Evidence indicates that leptin may have either adverse or beneficial effects on

175 These data revealed that leptin may regulate synaptic transmission in the LHA-to-

176 elective requirement of the AT1A receptor in leptin-mediated control of RMR.

177 Surprisingly, all mice responded normally to leptin-mediated euglycemia restoration, which was associ

178 t suppression of lipolysis is a key facet of leptin-mediated restoration of euglycemia.

179 -enriched islets isolated from diabetic BTBR Leptin(ob/ob) mice produced significantly less PGE2 and

180 are susceptible to obesity via dysregulated leptin/Ob-R signaling, whereas the lack of HDC protects

181 fects of triiodothyronine (T3 ), insulin and leptin on beta cell proliferation rates were determined

182 sed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca(2+) ]i handling and cell

183 iet feeding dampen the suppressive effect of leptin on synaptic transmission.

184 arding the adverse and beneficial effects of leptin on the heart We analysed the effect of a non-hype

185 asma concentrations were not associated with leptin or adiponectin.

186 In vitro studies using Leptin or DCA-treatment suggested causal significance of

187 gy and glucose homeostasis downstream of the leptin-PI3K pathway in POMC neurons.

188 Moreover, leptin potentiated NMDAR currents and triggered NMDAR-de

189 In conclusion, a higher log leptin pregnancy baseline concentration and a lower HDL-

190 al nervous system (CNS) and hormones such as leptin produced by adipocytes as well as other cells.

191 o alter both Lep transcript accumulation and leptin protein secretion, and may play a role in the sex

192 nscript abundance and cytosolic and secreted leptin protein.

193 Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants

194 pid GE, we studied mice with mutation of the leptin receptor (Lepr(db/db)), which in our colony had a

195 o major neurotransmitters in the brain, from leptin receptor (LepR) neurons, we used mice with disrup

196 ing conformation between mutant LEP(I14) and LEPTIN receptor (LEPR) suggests that the conformation of

197 es have suggested that MSPCs are observed as leptin receptor (LepR)-positive cells, whereas osteoblas

198 Leptin, leptin receptor (long isoform), and PTH mRNA transcripts

199 Leptin receptor (Ob-R) was evaluated by quantitative PCR

200 uction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglob

201 r the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1.

202 of metabolic syndrome attributable to double-leptin receptor defect (obese ZSF1) with the combined tr

203 ow that adult zebrafish lacking a functional leptin receptor do not exhibit hyperphagia or increased

204 sed in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/ST

205 egulatory effects of leptin depend on intact leptin receptor signaling.

206 , whereas no such association was found with leptin receptor, adiponectin, or C-reactive protein.

207 shown higher affinity upon binding with the leptin receptor, and similarly to native hormone activat

208 Materials and Methods In this study, 20 leptin receptor-deficient and three MPO knockout mice we

209 Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective c

210 We report that leptin receptor-expressing neurons (LepRb neurons) in th

211 Mechanistically, we found that attenuated leptin-receptor (LEPR) expression is essential for the d

212 n the arcuate nucleus are GABAergic, express leptin receptors (LepR), and are known to influence repr

213 bserved that AT1A receptors colocalized with leptin receptors (LEPRs) in the ARC.

214 with enhanced signaling through insulin and leptin receptors in animal models of diet-induced obesit

215 he native leptin and LepNPEG5K and activated leptin receptors in hypothalamus at lower dose than nati

216 halamo-pituitary-gonadal axis is mediated by leptin receptors on AgRP neurons.

217 At TNZ, leptin reduced food intake (-11.0 +/- 0.5 g cumulative d

218 Leptin reduced plasma glucose and insulin levels at 15 d

219 reated sham animals, whereas, following TAC, leptin reduced the APD towards control values.

220 hoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both me

221 Thus, the brain circuits by which leptin regulates food intake and cardiovascular function

222 Since leptin regulates inflammation, the beneficial effects of

223 Together, these data show that leptin regulates synaptic transmission and might be impo

224 erestingly, energy states seem to affect how leptin regulates synaptic transmission since both the de

225 oluntary physical activity and dopamine- and leptin-related gene expression.

226 In line, leptin release from isolated adipocytes was reduced, and

227 ned the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced r

228 eptin signaling attributable to diet-induced leptin resistance is associated with infertility in huma

229 velopment of treatment effectively targeting leptin resistance may benefit patients with atypical dep

230 roach to ameliorate diet-induced obesity and leptin resistance.

231 thening the hypothesis of the involvement of leptin resistance.

232 ate that the F4 obesity is consistent with a leptin resistant, thrifty phenotype.

233 nstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin and incr

234 s body fat mass independently of fat-derived leptin, revealing two independent negative feedback syst

235 The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown.

236 e acute insulin-independent effects by which leptin reverses fasting hyperglycemia and ketoacidosis i

237 rsus the chronic pleotropic effects by which leptin reverses hyperglycemia in a non-DKA rodent model

238 P, but whether this regulation overlaps with leptin's actions is unclear.

239 In the DIO mice, JNK inhibition sensitized leptin's anorectic effect, and enhanced leptin-induced S

240 Conversely, cold TA caused resistance to leptin's anorexic effects but amplified its effects to r

241 These actions appear to be independent of leptin's metabolic effects.SIGNIFICANCE STATEMENT Sexual

242 Based on leptin's recently discovered role in bone metabolism, we

243 heterologous cell system, we show that human leptin secretion is also regulated by Ca(2+) and CaMKII.

244 ytic rate and alterations in adiponectin and leptin secretion.

245 ation at the Arc-ME diffusion barrier, a new leptin-sensing neuron population, multiple agouti-relate

246 rator for RMR control through its actions at leptin-sensitive AgRP cells of the ARC.

247 In vivo, leptin sensitivity is substantially impaired in HDAC5 lo

248 -kappaB pathway while restoring hypothalamic leptin sensitivity.

249 compound, withaferin A, that also acts as a leptin sensitizer.

250 Furthermore, leptin shows circadian variation in its circulating leve

251 Furthermore, the leptin signal transduction in hypothalamus was improved

252 Obesity-related dysregulation of leptin signaling (e.g., hyperleptinemia due to central f

253 PTP1B is a negative regulator of insulin and leptin signaling and a highly validated therapeutic targ

254 nalysis revealed ovarian steroidogenesis and leptin signaling as highly relevant in domestication.

255 Deficient leptin signaling attributable to diet-induced leptin res

256 that in females, the absence of AgRP neuron leptin signaling delays puberty.

257 These results indicate that leptin signaling in AgRP neurons is sufficient for puber

258 chicken leptin gene has hampered research of leptin signaling in this species for almost two decades.

259 We also present findings that implicate leptin signaling in uridine homeostasis and consequent m

260 nd normal adult fecundity in both sexes when leptin signaling is absent in all other cells and that i

261 HDC/histamine/leptin signaling may be important in managing obesity-in

262 ggesting a variant-mediated dysregulation of leptin signaling may play a role in AN.

263 ary proliferation and fibrosis and regulates leptin signaling.

264 d db/db mice, both of which are deficient in leptin signaling.

265 adipocyte-dependent uridine biosynthesis and leptin signaling.

266 ypothalamic HDAC5 activity is a regulator of leptin signalling that adapts food intake and body weigh

267 nervous system regulation of food intake and leptin signalling.

268 sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E

269 Furthermore: 1) Leptin stimulated PRL/ACTH/FSH- but not LH/TSH-release;

270 er, while high concentrations of insulin and leptin stimulated proliferation.

271 elineate closure of this critical period for leptin-stimulated growth, we treated Lep(ob/ob) mice wit

272 loping hypothalamus, the fat-derived hormone leptin stimulates the growth of axons from the arcuate n

273 Taken together, leptin substitution was accompanied by long-term changes

274 The high GC-content observed for the chicken leptin syntenic group suggests that other similar cluste

275 We compared this conjugate with the native leptin, the N-terminal leptin conjugate with poly(ethyle

276 ripts encoding leptin and increased secreted leptin to 230% of the control.

277 king NMDAR activity inhibited the ability of leptin to activate AMPK, induce KATP and Kv2.1 channel t

278 s have a key role in mediating the effect of leptin to modulate beta-cell electrical activity by prom

279 Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores.

280 oup (79%), lower proinflammatory adipokines (leptin-to-adiponectin ratio) (73%), and much lower proth

281 Mapping chicken leptin together with a cluster of five syntenic genes pr

282 f action potential duration (APD) in TAC and leptin-treated sham animals, whereas, following TAC, lep

283 Furthermore, leptin treatment for 9 days or more was sufficient to re

284 the present study, we analysed the effect of leptin treatment on cardiac function, [Ca(2+) ]i handlin

285 the present study demonstrate that, although leptin treatment was deleterious on cardiac function in

286 iographic measurements showed that, although leptin treatment was deleterious on cardiac function in

287 his phenotype is largely rescued by neonatal leptin treatments.

288 nfocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells.

289 Among currently depressed patients, higher leptin was associated with key symptoms identifying the

290 As compared to control subjects, higher leptin was associated with the atypical MDD subtype both

291 No association with leptin was found for overall MDD or the typical subtype.

292 ng and sequence characteristics, the chicken leptin was not located on a microchromosome, which are k

293 Pregnancy baseline concentration of log leptin was positively associated (OR = 3.92; p = 0.025)

294 re induced obesity (e.g., increased insulin, leptin, weight, and percent body fat) in the Long-Evans,

295 I, triglycerides, cholesterol, cortisol, and leptin, were measured after an overnight fast.

296 tude of this effect was greatest on secreted leptin, which was decreased by DHT to 30% of the control

297 We examined the relationship of leptin with MDD, its common subtypes (typical and atypic

298 Compared to the random conjugates of leptin with P85, LepNP85 has shown higher affinity upon

299 problem, we modified the N-terminal amine of leptin with Pluronic P85 (LepNP85) and administered this

300 e glycol) (LepNPEG5K), and two conjugates of leptin with Pluronic P85 attached randomly to the lysine