Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice

Lee, Young-Sil; Cha, Byung‐Yoon; Choi, Sooyoung; Choi, Bong‐Keun; Yonezawa, Takayuki; Teruya, Toshiaki; Nagai, Kazuo; Woo, Je‐Tae

doi:10.1016/j.jnutbio.2012.03.014

Cited by 153 publications

(100 citation statements)

References 38 publications

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“…It seems that one of the major differences between DIO and leptin signalingdeficient obesity due to PEG-SMLA treatment is the inflammatory condition. Circulating inflammatory cytokines are higher in DIO compared with normal subjects (18,53,59,69). With respect to leptin signaling, we showed that chronic inflammation is alleviated in leptin antagonist-treated mice (26,27); this might explain the differences found in bone phenotype between the two models.…”

Section: E22 Leptin Inhibition Effect On Metabolic and Bone Phenotypesmentioning

confidence: 70%

“…with the HFD (18,21,53,59), whereas in the PEG-SMLA treatment it was unchanged after 4 wk and increased 4.8-fold after 12 wk. However, in a shorter PEG-SMLA treatment with murine urokinase-like plasminogen activator (␣MUPA) and FVB/N (WT) mice, the blood level of those cytokines was not significantly changed (16).…”

Section: E22 Leptin Inhibition Effect On Metabolic and Bone Phenotypesmentioning

confidence: 90%

“…A comparison of two inflammatory cytokines showed a similar pattern. IL-6 increased 1.4-to fivefold in HFD after 5-24 wk (18,53,69), whereas with the PEG-SMLA treatment it increased 1.6-fold after 12 wk. TNF␣ increased two-to fourfold after 5-15 wk …”

Section: E21 Leptin Inhibition Effect On Metabolic and Bone Phenotypesmentioning

confidence: 91%

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Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse

Solomon¹,

Atkins

Shahar

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Leptin's in vivo effect on the rodent skeleton depends on the model used and the mode of administration. Superactive mouse leptin antagonist (SMLA) was produced and then pegylated (PEG) to prolong and enhance its in vivo activity. We blocked leptin signaling by injecting this antagonist peripherally into normal mice at various time points and studied their metabolic and skeletal phenotypes. Subcutaneous PEG-SMLA injections into 4-wk-old female C57BL/6J mice increased weight gain and food consumption significantly after only 1 mo, and the effect lasted for the 3 mo of the experiment, proving its central inhibiting activity. Mice showed a significant increase in serum glucose, cholesterol, triglycerides, insulin, and HOMA-IR throughout the experiment. Quantification of gene expression in "metabolic" tissues also indicated the development of insulin resistance. Bone analyses revealed a significant increase in trabecular and cortical parameters measured in both the lumbar vertebrae and tibiae in PEG-SMLA-treated mice in the 1st and 3rd months as well as a significant increase in tibia biomechanical parameters. Interestingly, 30 days of treatment with the antagonist in older mice (aged 3 and 6 mo) affected body weight and eating behavior, just as they had in the 1-mo-old mice, but had no effect on bone parameters, suggesting that leptin's effect on bones, either directly or through its obesogenic effect, is dependent upon stage of skeletal development. This potent and reversible antagonist enabled us to study leptin's in vivo role in whole body and bone metabolism and holds potential for future therapeutic use in diseases involving leptin signaling. leptin signaling; insulin resistance; microcomputed tomography; obesity LEPTIN, A 16-KDA PROTEIN, is a central regulator of body weight (BW) (32) as well as a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and immune response modulation. Obesity is associated with increased leptin synthesis and secretion, whereas fasting and weight loss are associated with decreased leptin synthesis and secretion. Leptin acts through both central and peripheral mechanisms to affect feeding behavior, lipid and glucose metabolism, thermogenesis, reproductive and endocrine functions, and cardiovascular and immune functions (32). The extent of leptin's actions can be seen in ob/ob mice that lack leptin in circulation. These mice are obese, diabetic, and sterile and exhibit reduced activity, metabolism, and body temperature. All of these phenotypes can be rescued by daily injection of leptin.In addition, leptin is a major regulator of bone metabolism, but data are contradictory regarding its effects on bone mass in rodents. Several studies have described leptin-deficient ob/ob mice as having high bone mass (4, 24, 46), and intracerebroventricular injections of leptin decrease bone mass in both ob/ob mice and lean rodents (25). Others have observed lower bone mass in leptin-deficient mi...

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Section: E22 Leptin Inhibition Effect On Metabolic and Bone Phenotypesmentioning

confidence: 70%

Section: E22 Leptin Inhibition Effect On Metabolic and Bone Phenotypesmentioning

confidence: 90%

See 1 more Smart Citation

Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse

Solomon¹,

Atkins

Shahar

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…It is well documented that dysregulation of hypothalamus pituitary adrenal (HPA) axis results in excessive cortisol release in the circulation and finally to "insulin resistance" or "altered glucose level" as observed in depressed and obese subjects (Brown et al, 2004). Furthermore, obesity is one of the serious public health concern where insulin resistance or altered plasma glucose holds the key and is characterized by dysregulation of lipids (Kahn and Flier, 2000;Lee et al, 2013). Earlier reports suggested the association of dyslipidemia and obesity with the individuals reflecting more depressive and anxiety-like behavior (van Reedt Dortland et al, 2010b).…”

Section: Discussionmentioning

confidence: 99%

QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice: An approach based on behavioral and biochemical investigations

Kurhe

Mahesh

Gupta

et al. 2014

European Journal of Pharmacology

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“…In consideration of these observations, the effects of aculeatin seem to resemble those of nobiletin, but not Pio. Because Lee et al showed that nobiletin could improve hyperglycemia, obesity and insulin resistance in animal studies [15,16], we can anticipate that aculeatin also may exert these effects in vivo. The latter assumption is currently undergoing investigation in our laboratory.…”

Section: Discussionmentioning

confidence: 96%

Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes

Watanabe

Kato

Ito

et al. 2014

Biochemical and Biophysical Research Communications

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Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice

Cited by 153 publications

References 38 publications

Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse

Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse

QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice: An approach based on behavioral and biochemical investigations

Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes

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