Adiponectin acts in the brain to decrease body weight.

Yong Qi; Nobuhiko Takahashi; Stanley M Hileman; Hiralben R Patel; Anders H Berg; Utpal B Pajvani; Philipp E Scherer; Rexford S Ahima

doi:10.1038/nm1029

PubMed · 15077108

Adiponectin acts in the brain to decrease body weight.

Yong Qi·Nobuhiko Takahashi·Stanley M Hileman·Hiralben R Patel·Anders H Berg·Utpal B Pajvani·Philipp E Scherer·Rexford S Ahima

View original source ↗Export metadata ↓

Abstract

Adiponectin (ADP) is an adipocyte hormone involved in glucose and lipid metabolism. We detected a rise in ADP in cerebrospinal fluid after intravenous (i.v.) injection, consistent with brain transport. In contrast to leptin, intracerebroventricular (i.c.v.) administration of ADP decreased body weight mainly by stimulating energy expenditure. Full-length ADP, mutant ADP with Cys39 replaced with serine, and globular ADP were effective, whereas the collagenous tail fragment was not. Lep(ob/ob) mice were especially sensitive to i.c.v. and systemic ADP, which resulted in increased thermogenesis, weight loss and reduction in serum glucose and lipid levels. ADP also potentiated the effect of leptin on thermogenesis and lipid levels. While both hormones increased expression of hypothalamic corticotropin-releasing hormone (CRH), ADP had no substantial effect on other neuropeptide targets of leptin. In addition, ADP induced distinct Fos immunoreactivity. Agouti (A(y)/a) mice did not respond to ADP or leptin, indicating the melanocortin pathway may be a common target. These results show that ADP has unique central effects on energy homeostasis.

Explore related subjects

Adiponectin Agouti Signaling Protein Animals Body Weight Brain Drug Synergism Energy Metabolism Injections, Intraventricular Intercellular Signaling Peptides and Proteins Leptin Mice Mice, Inbred C57BL Mice, Mutant Strains Mice, Obese Proteins Recombinant Proteins Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Yong Qi, Nobuhiko Takahashi, Stanley M Hileman, Hiralben R Patel, Anders H Berg, Utpal B Pajvani, Philipp E Scherer, Rexford S Ahima. 2004-04-11. Adiponectin acts in the brain to decrease body weight.. https://doi.org/10.1038/nm1029

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

The benefits of early intervention in obese diabetic patients with FBCx: a new dietary fibre.

BACKGROUND: Obesity and diabetes have become epidemic in the US. Dietary fibres have been reported to reduce the absorption of dietary fat, prevent weight gain, and reduce blood lipid levels. In the current double-blind study, obese patients with type 2 diabetes were recruited for a 3-month study to examine the health effects of a new dietary fibre, FBCx. METHODS: Sixty-six participants were recruited and were randomized into FBCx or placebo groups. They were instructed to take two 1-g tablets per fat-containing meal and not to change their eating patterns or daily routine. Three-day dietary records and fasting blood samples were collected prior to enrollment in the study and at the end of months 1, 2 and 3. RESULTS: Dietary records showed that some participants changed their eating patterns; therefore body weight data were adjusted according to energy intake. As a group, in the 30 days leading into the study, all participants experienced an average weight gain of 1.0 +/- 0.4 kg, while those in the placebo group continued to gain weight during the study, those in the FBCx group maintained their weight. Those in the FBCx group required more energy to maintain their body weight while those in the placebo group required less (p < 0.05). Participants with hypertriglyceridemia showed a reduction (-0.48 +/- 0.24 mmol/L, - 8.2%) in total cholesterol with FBCx, while those with placebo had an increase (0.24 +/- 0.21 mmol/L, 5.2%, p < 0.05). Adiponectin was increased in the FBCx but reduced in the placebo group (p < 0.05). CONCLUSIONS: FBCx has thus shown promising benefits in weight maintenance, a reduction of blood lipids and an increase in adiponectin levels. It can be easily incorporated into a diabetic management regimen.

Adiponectin↗

PubMed2007

Plasma levels of interleukin-6 and C-reactive protein are associated with physical inactivity independent of obesity.

It is recognized that the path from physical inactivity and obesity to lifestyle-related diseases involves low-grade inflammation, indicated by elevated plasma levels of inflammatory markers. Interestingly, contracting skeletal muscle is a major source of circulating interleukin-6 (IL-6) in response to acute exercise, but with a markedly lower response in trained subjects. As C-reactive protein (CRP) is induced by IL-6, we hypothesized that basal levels of IL-6 and CRP reflect the degree of regular physical activity when compared with other markers of inflammation associated with lifestyle-related morbidity. Fasting plasma/serum levels of IL-6, IL-18, CRP, tumur necrosis factor-alpha (TNF-alpha), soluble TNF receptor II (sTNF-RII), and adiponectin were measured in healthy non-diabetic men and women (n=84). The amount of leisure-time physical activity (LTPA) was assessed by interview. Obesity was associated with elevated insulin, C-peptide, triglycerides, low-density lipoprotein, IL-6, CRP, and adiponectin (all P<0.05). Importantly, physical inactivity was associated with elevated C-peptide (P=0.036), IL-6 (P=0.014), and CRP (P=0.007) independent of obesity, age, gender, and smoking. Furthermore, the LTPA score was inversely associated with IL-6 (P=0.017) and CRP (P=0.005), but with neither of the other markers. The results indicate that low levels of IL-6 and CRP - not IL-18, TNF-alpha, sTNF-RII, or adiponectin - reflect regular physical activity.

Adiponectin↗

PubMed2006

Aging influences the level and functions of fasting plasma ghrelin levels: the POWIRS-Study.

OBJECTIVE: Ghrelin, known for its orexigenic activity, also have functions such as vasodilation and a growth hormone releasing action. It is uncertain whether these functions change with increasing age. This study aimed to determine whether ghrelin levels differ between young and older women with different levels of obesity; and secondly whether the associations of ghrelin with metabolic syndrome (MS) components, adipocytokines, coagulation factors, and cortisol change with increasing age. METHODS AND RESULTS: Caucasian women (N=107) were divided into young (19-29 years) and older groups (30-56 years). Fasting ghrelin, leptin, adiponectin, glucose, insulin, cortisol, fibrinogen and plasminogen activator inhibitor-1 (PAI-1) levels were determined. Blood pressure (BP), body mass index and waist circumferences were measured. Older lean women showed lower levels of ghrelin (p<0.05) than young lean women, with no differences regarding BP, obesity, lipids, adipokines or insulin resistance (IR). Ghrelin levels of older women remained constant with increasing obesity, but younger women showed significantly reduced ghrelin levels in obese groups. Only younger women showed significant correlations between ghrelin and leptin, adiponectin, fibrinogen and PAI-1 (adjusted for age, obesity and menstrual phase), whereas both age groups showed significant correlations with IR. In younger women factor analysis grouped ghrelin with coagulation factors and all MS components. In older women ghrelin was absent from the MS cluster, but was associated with lower BP, cortisol and IR. CONCLUSIONS: Ghrelin levels were not significantly elevated in lean older women, and did not change with increased obesity in older women--as were observed in younger women. The functions of ghrelin also seem to change with increased age since only in young women ghrelin was associated with obesity, coagulation factors and leptin.

Adiponectin↗