Hepatic adipoR2 Research Articles

Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Exercise ameliorates high-fat diet-induced insulin resistance accompanied by changes in protein levels of hepatic ATF3-related signaling in rats

PurposeExercise is an effective way to alleviate insulin resistance (IR). However, the underlying mechanisms remain to be elucidated. Previous studies demonstrated that cardiolipin synthase 1 (CRLS1)/interferon-regulatory factor-2 binding protein 2 (IRF2bp2)-activating transcription factor 3 (ATF3)-adiponectin receptor 2 (AdipoR2)-adaptor protein containing pH domain, PTB domain and leucine zipper motif 1 (APPL1)-protein kinase B (AKT/PKB)-related signaling was closely associated with obesity-induced IR-related diseases, but the correlation between exercise training alleviating obesity-induced IR and the protein levels of hepatic CRLS1/IRF2bp2-ATF3-AdipoR2-APPL1-AKT-related signaling in rats is unknown. Therefore, We want to investigate the effect of exercise training on IR and the protein levels of hepatic CRLS1/IRF2bp2-ATF3-AdipoR2-APPL1-AKT-related signaling in rat. MethodsThe male healthy Sprague-Dawley rats were divided into four groups: normal control group (NCG, n = 10), diet-induced obesity-sedentary group (DIO-SG, n = 10), diet-induced obesity-chronic exercise group (DIOCEG, n = 10) received chronic swim exercise training and diet-induced obesity-acute exercise group (DIO-AEG, n = 10) received acute swim exercise training. We measured the levels of IR-related indicators and the protein levels of hepatic CRLS1/IRF2bp2-ATF3-AdipoR2-APPL1-AKT-related signaling in NCG, DIO-SG, DIOCEG and DIO-AEG. ResultsWe found that high-fat diet (HFD)-induced obesity decreased insulin sensitivity in rats accompanied by decreased protein levels of hepatic CRLS1, IRF2bp2, AdipoR2, APPL1, p-AKT and increased protein level of hepatic ATF3. The acute exercise and the chronic exercise both increased insulin sensitivity in rats. The chronic exercise decreased hepatic ATF3 protein level and increased CRLS1, IRF2bp2, AdipoR2, APPL1, p-AKT protein levels in HFD-fed rats. The acute exercise decreased hepatic ATF3 protein level and increased hepatic IRF2bp2, APPL1 and p-AKT protein levels in HFD-fed rats. The acute exercise had no significant effect on hepatic CRLS1 and AdipoR2 protein levels in HFD-fed rats. ConclusionOur current findings indicated that exercise alleviated obesity-induced IR accompanied by changes in protein levels of hepatic ATF3-related signaling in rats. Our results are meaningful for exploring the molecular mechanism of exercise alleviating IR symptoms.

Long-term supplementation of esculetin ameliorates hepatosteatosis and insulin resistance partly by activating AdipoR2–AMPK pathway in diet-induced obese mice

The effects of esculetin on hepatosteatosis and insulin resistance in high-fat diet (HFD)-induced obese mice were investigated. Esculetin (0.02%, w/w) provided to mice fed a HFD (40% kcal from fat) for 12 weeks reduced body weight gain, visceral adiposity, hepatosteatosis, hyperlipidemia and hyperglycemia, whereas it increased plasma adiponectin level and the protein and mRNA expression of hepatic AdipoR2, which led to the activation of AMPK. The protein and mRNA expression of hepatic PPARα were up-regulated by esculetin and those of SREBP-1c were down-regulated. Esculetin elevated expression of hepatic fatty acid oxidation genes (PGC-1α, PPARα, Acsl1 and CPT), while suppressing expression of fatty acid synthesis gene. Anti-insulin resistant effects of esculetin were mediated by increased hepatic GLUT2 and glucokinase mRNA levels and decreased glucose-6-phosphatase mRNA level. These findings suggest that esculetin supplementation has beneficial effects on hepatosteatosis and insulin resistance in HFD-induced obese mice, partly via activation of the AdiopR2–AMPK pathway.

The effects of LPS-induced endotoxemia on the expression of adiponectin and its receptors in female rats.

Adiponectin (APN), secreted by white adipose tissue (WAT), acts as a protective factor against inflammatory conditions. However, the changes in the expression levels of endogenous APN and the two types of APN receptor (AdipoR1 and AdipoR2) induced by acute inflammatory conditions have not been fully elucidated. In this study, the changes in peripheral and/or central APN and AdipoR expression caused by lipopolysaccharide (LPS)-induced sepsis were examined in gonadal-intact (Sham) and ovariectomized (OVX) female rats. As it has been reported that APN and AdipoR suppress the production of inflammatory cytokines to prevent excessive inflammation, the mRNAs of these molecules were also examined. LPS injection induced increases in visceral WAT APN mRNA without affecting the serum APN level in both the Sham and OVX rats. OVX rats exhibited higher serum APN levels than Sham rats. LPS injection increased the subcutaneous WAT APN mRNA in OVX rats. In both Sham and OVX rats, LPS injection led to a decrease in hepatic AdipoR2 mRNA and an increase in hypothalamic AdipoR2 mRNA. Hypothalamic AdipoR2 mRNA was upregulated 24 h after LPS injection in OVX but not Sham rats. Serum TNF-α level at 6 h after LPS injection and hypothalamic and hepatic IL-6 and TNF-α mRNA at 24 h after LPS injection were significantly higher in Sham than OVX rats. These results suggest that APN and AdipoR play roles in modulating inflammation under septic conditions in female rats.

Role of SIRT1-FoxO1 Signaling in Dietary Saturated Fat-Dependent Upregulation of Liver Adiponectin Receptor 2 in Ethanol-Administered Mice

The aim of the present study is to examine the effects of dietary saturated fatty acids on liver adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2) in ethanol-administered animals and in ethanol-exposed cultured hepatic cells, and to explore the underlying molecular mechanisms. The mRNA and protein levels of hepatic AdipoR2 were selectively increased by chronic ethanol feeding to mice consuming a diet high in saturated fat (HSF). Administration of an HSF diet blocked hyperacetylation of forkhead transcription factor 1 (FoxO1), a known target of sirtuin 1 (SIRT1), increased nuclear FoxO1 protein levels, and enhanced association of FoxO1 with the AdipoR2 promoter in the livers of ethanol-fed mice. Treatment of cultured hepatic cells with palmitic acid (a major saturated fatty acid in HSF diet) in the presence of ethanol robustly increased AdipoR2 mRNA expression and enhanced activity of a mouse AdipoR2 promoter. Knocking down SIRT1 or FoxO1 using the small silencing SIRT1 or FoxO1 plasmid blunted the palmitic acid effect. Taken together, these results reveal that dietary saturated fat selectively upregulates hepatic AdipoR2 through modulation of SIRT1-FoxO1 signaling in ethanol fed mice, and this effect may contribute to the protective effect of the HSF diet against alcoholic fatty liver.

Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

BackgroundGrowth hormone (GH) is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy) could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD) and explored the underlying molecular mechanisms.MethodsMale C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW) adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism.ResultsSerum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P < 0.001). GH1 therapy reversed HMW adiponectin levels to the normal levels in the alcohol-fed group. Alcohol feeding significantly reduced hepatic adipoR2 mRNA expression compared with that in the control group (0.71 ± 0.17 vs. 1.03 ± 0.19; P < 0.001), which was reversed by GH therapy. GH1 therapy also significantly increased the relative mRNA (1.98 ± 0.15 vs. 0.98 ± 0.15) and protein levels of SIRT1 (2.18 ± 0.37 vs. 0.99 ± 0.17) in the alcohol-fed group compared with those in the control group (both, P < 0.001). The alcohol diet decreased the phosphorylated and total protein levels of hepatic AMP-activated kinase-α (AMPKα) (phosphorylated protein: 0.40 ± 0.14 vs. 1.00 ± 0.12; total protein: 0.32 ± 0.12 vs. 1.00 ± 0.14; both, P < 0.001) and peroxisome proliferator activated receptor-α (PPARα) (phosphorylated protein: 0.30 ± 0.09 vs. 1.00 ± 0.09; total protein: 0.27 ± 0.10 vs. 1.00 ± 0.13; both, P < 0.001), which were restored by GH1 therapy. GH therapy also decreased the severity of fatty liver in alcohol-fed mice.ConclusionsGH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

Hepatic adiponectin receptor R2 expression is up-regulated in normal adult male mice by chronic exogenous growth hormone levels

Previous studies investigating the effects of exogenous growth hormone (GH) on the expression of adiponectin and the adiponectin receptors have generated seemingly conflicting results. Here, to determine the effects of chronic exogenous GH levels, we investigated the expression of adiponectin receptor R1 (adipoR1) in skeletal muscle and adiponectin receptor R2 (adipoR2) in the liver of normal C57BL/6 adult male mice 24 weeks after a single injection of rAAV2/1-CMV-GH1 viral particles. AdipoR1 and adipoR2 mRNA expression levels were determined by quantitative real-time reverse transcription-polymerase chain reaction. AdipoR1 and adipoR2 proteins were analyzed by Western blotting. Serum total and high molecular weight (HMW) adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) kits for mice. The results demonstrated that the injection of rAAV2/1-CMV-GH1 within the concentration range of 1.0x1011 to 4.0x1011 viral particles significantly up-regulated hepatic adipoR2 gene expression. The serum HMW adiponectin level increased significantly with the concentration range of 2.0x1011 to 4.0x1011 rAAV2/1-CMV-GH1 viral particles. The injection of 4.0x1011 rAAV2/1-CMV-GH1 viral particles induced a significant increase in both serum glucose and insulin concentrations (p<0.05), and the homeostasis model assessment of insulin resistance (p<0.01). This may decrease body insulin sensitivity and therefore raise the potential risk of insulin resistance. However, exogenous GH levels did not significantly affect adipoR1 expression in skeletal muscle. In conclusion, chronic exogenous GH up-regulates hepatic adipoR2, rather than adipoR1, in vivo, and raises the serum HMW adiponectin level. However, the elevation of exogenous GH concentrations may increase the risk of insulin resistance.

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

Adiponectin signalling attenuates insulin resistance (IR) and steatosis hepatis in animal models. As adiponectin receptor (ADIPOR)1 and ADIPOR2 are critical components in the adiponectin signalling cascade, we studied hepatic ADIPOR1/2 mRNA levels in humans and their relation to IR. We determined metabolic risk factors and levels of hepatic mRNA transcribed from ADIPOR1, ADIPOR2 and FOXO1, a putative up-stream regulator, in 43 and 34 obese subjects with low and high homeostasis model assessment-IR, respectively. Plasma adiponectin and metabolic risk factors showed associations with IR as expected. Both hepatic ADIPOR1 and ADIPOR2 mRNA expression levels were higher in insulin-resistant subjects (P<0.0035). ADIPOR1 mRNA correlated with FOXO1 mRNA in obese insulin resistant (P=0.0034), but not insulin-sensitive subjects, while no correlations of ADIPOR2 with FOXO1 mRNA were noted. FOXO1 enhanced transcription from the ADIPOR1, but not the ADIPOR2 promoter in HepG2 cells. Increased hepatic ADIPOR1 and ADIPOR2 mRNA in insulin-resistant obese subjects may, at least in part, reflect a compensatory mechanism for reduced plasma adiponectin. FOXO1 may contribute to enhanced ADIPOR1, but not ADIPOR2 transcription in IR.

The role of adiponectin and adiponectin receptor 2 in the pathology of fatty liver

To investigate the role of adiponectin (ADP) and adiponectin receptor 2 (adipoR2) in pathology of fatty liver, and to investigate the effect of Chinese herbal decoction (Qushi Huayu Decoction, QHD) on fatty liver disease. Two experimental fatty liver models were used. One was induced with high-fat diet for ten weeks, and the rats were divided into normal, model and QHD group, the QHD group was administrated with QHD during the last four weeks. The other experimental fatty liver model was induced by subcutaneous injection of carbon tetrachloride (CCl4) in combination with high-fat and low-protein diet for four weeks, and the rats were also divided into normal, model and QHD group, the QHD group was administrated with QHD during the last two weeks. The observation items include: (1) hepatic steatosis (H.E. staining); (2) serum ADP, hepatic triglyceride (TG), free fatty acid (FFA) and adipoR2; (3) correlation among serum ADP content, hepatic TG, FFA and adipoR2. (1) Serious hepatic steatosis, increased hepatic TG and FFA, decreased serum ADP and hepatic adipoR2 were observed in the two models (P less than 0.01). QHD administration significantly reduced the hepatic TG and FFA, and increased serum ADP and hepatic adipoR2 (P less than 0.01) in these two models. (2) Inverse correlation was observed between hepatic TG, FFA and serum ADP, hepatic adipoR2 in these two models. (1) Decreased serum ADP and hepatic adipR2 may play important roles in pathological process of fatty liver. (2) QHD administration increased the serum ADP and hepatic adipoR2.

Adiponectin receptor 2 is regulated by nutritional status, leptin and pregnancy in a tissue-specific manner

The aim of the present work was to study the regulation of circulating adiponectin levels and the expression of adiponectin receptor 2 (Adipo-R2) in several rat tissues in relation to fasting, leptin challenge, pregnancy, and chronic undernutrition. Using real-time PCR, we found Adipo-R2 mRNA expression in the liver, stomach, white and brown adipose tissues (WAT and BAT) of adult rats. Immunohistochemical studies confirmed protein expression in the same tissues. Adipo-R2 mRNA levels were decreased in liver after fasting, with no changes in the other tissues. Leptin decreased Adipo-R2 expression in liver and stomach, but increased its expression in WAT and BAT. Chronic caloric restriction in normal rats increased Adipo-R2 gene expression in stomach, while it decreased hepatic Adipo-R2 levels in pregnant rats. Using radioimmunoassay, we found that plasma adiponectin levels were diminished by fasting and leptin. Conversely, circulating adiponectin was increased in food-restricted rats, whereas its levels decreased in food-restricted pregnant rats by the end of gestation. In conclusion our findings provide the first evidence that (a) Adipo-R2 mRNA is regulated in a tissue-specific manner by fasting, but leptin is not responsible for those changes; (b) chronic caloric restriction in normal and pregnant rats also regulate Adipo-R2 mRNA in a tissue-specific manner; and (c) Adipo-R2 mRNA does not show a clear correlation with plasma adiponectin levels.

ANGIOTENSIN‐CONVERTING ENZYME INHIBITORS IMPROVE HEPATIC STEATOSIS BY MODULATING EXPRESSION OF TUMOUR NECROSIS FACTOR‐α, INTERLEUKIN‐6 AND ADIPONECTIN RECEPTOR‐2 IN RATS WITH TYPE 2 DIABETES

1. Angiotensin-converting enzyme inhibitors (ACEI) are hypotensive drugs that have been shown to prevent Type 2 diabetes mellitus (T2DM) in high-risk individuals. However, in T2DM, the effects of ACEI on hepatic steatosis are not known. The aim of the present study was to examine the effects of ACEI on changes in liver histology and hepatic mRNA expression of adipokines in rats with T2DM. 2. Thirty-six rats were divided into a normal control group, a T2DM group and a fosinopril-treated group. After six weeks of treatment with 5 mg/kg per day fosinopril, an ACEI, changes in liver histology, serum fasting glucose (FG), insulin, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin were evaluated, as was hepatic TNF-alpha, IL-6 and adiponectin receptor-2 (adipoR2) mRNA expression. 3. The degree of hepatic steatosis and inflammation, serum FG, insulin, TG, TC, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression were significantly higher in rats with T2DM than in normal controls. Serum adiponectin concentrations and hepatic adipoR2 mRNA expression in rats with T2DM were significantly lower than in normal controls. Fosinopril significantly reduced the degree of hepatic steatosis, serum FG, insulin, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression. Fosinopril significantly increased serum adiponectin concentrations and hepatic adipoR2 mRNA expression. 4. In conclusion, the ACEI improved insulin sensitivity and hepatic steatosis in rats with T2DM by increasing circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokine levels in the circulation and liver.

Effects of probucol on hepatic tumor necrosis factor‐α, interleukin‐6 and adiponectin receptor‐2 expression in diabetic rats

Probucol is a lipid-lowering agent with anti-oxidant effects. Oxidative stress and inflammation are important in the pathophysiology of insulin resistance. We aimed to evaluate the effects of probucol on liver histological changes, serum and hepatic levels of adipokines in rats with high fat-induced type 2 diabetes (T2D). Thirty-six rats were divided into a normal control group, a high fat-induced T2D group and a probucol treatment group. After six weeks of treatment with probucol, we evaluated liver histological changes and measured homeostasis model assessment index (HOMA-IR), serum superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin and hepatic TNF-alpha, IL-6 and adiponectin receptor-2 (adipoR2) mRNA. The degree of hepatic steatosis and inflammation, HOMA-IR, serum ALT, TNF-alpha and IL-6 concentrations, and hepatic TNF-alpha and IL-6 mRNA expression in diabetic rats were significantly higher compared with normal controls. Serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression in diabetic rats were significantly lower compared with normal controls. Probucol significantly reduced the degree of hepatic steatosis, HOMA-IR, serum ALT, TNF-alpha and IL-6 concentrations, and hepatic TNF-alpha and IL-6 mRNA expression. Probucol significantly raised serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression. In rats with high fat-induced T2D, treatment with probucol improved insulin sensitivity, hepatic steatosis by raising circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokines in the circulation and liver.

Hepatic AdipoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice

It is unclear how hepatic adiponectin resistance and sensitivity mediated by the adiponectin receptor, AdipoR2, contributes to the progression of nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the roles of hepatic AdipoR2 in NASH, using an animal model. We fed C57BL/6 mice a methionine-deficient and choline-deficient (MCD) diet for up to 8 weeks and analyzed changes in liver pathology caused by either an AdipoR2 short hairpin RNA-expressing adenovirus or an AdipoR2-overexpressing adenovirus. Inhibition of hepatic AdipoR2 expression aggravated the pathological state of NASH at all stages: fatty changes, inflammation, and fibrosis. In contrast, enhancement of AdipoR2 expression in the liver improved NASH at every stage, from the early stage to the progression of fibrosis. Inhibition of AdipoR2 signaling in the liver diminished hepatic peroxisome proliferator activated receptor (PPAR)-alpha signaling, with decreased expression of acyl-CoA oxidase (ACO) and catalase, leading to an increase in lipid peroxidation. Hepatic AdipoR2 overexpression had the opposite effect. Reactive oxygen species (ROS) accumulation in liver increases hepatic production of transforming growth factor (TGF)-beta1 at all stages of NASH; adiponectin/AdipoR2 signaling ameliorated TGF-beta-induced ROS accumulation in primary cultured hepatocytes, by enhancing PPAR-alpha activity and catalase expression. The adiponectin resistance and sensitivity mediated by AdipoR2 in hepatocytes regulated steatohepatitis progression by changing PPAR-alpha activity and ROS accumulation, a process in which TGF-beta signaling is implicated. Thus, the liver AdipoR2 signaling pathway could be a promising target in treating NASH.

Effects of lactogen resistance and GH deficiency on mouse metabolism: pancreatic hormones, adipocytokines, and expression of adiponectin and insulin receptors

We recently described a novel mouse model that combines resistance to lactogenic hormones with GH deficiency (GHD). The GHD/lactogen-resistant males develop obesity and insulin resistance with age. We hypothesized that altered production of pancreatic hormones and dysregulation of adipocytokine secretion and action contribute to the pathogenesis of their insulin resistance. Double-mutant males (age 12-16 months) had fasting hyperinsulinemia, hyperamylinemia, hyperleptinemia, and a decreased ratio of adiponectin to leptin. Adiponectin receptor 1 and 2 (AdipoR1 and R2) mRNA levels in liver and skeletal muscle were normal but hepatic insulin receptor mRNA was increased. Relative to double-mutant males, GHD males had lower levels of insulin, amylin, and leptin, higher levels of adiponectin, and higher expression of hepatic AdipoR1 and insulin receptor mRNAs. Lactogen-resistant mice had reduced hepatic adipoR2 mRNA. In response to stress the plasma concentrations of MCP-1 and IL-6 increased in double-mutant males but not GHD or lactogen-resistant males. Our findings suggest that the insulin resistance of GHD/lactogen-resistant males is accompanied by dysregulation of pancreatic hormone and adipocytokine secretion and receptor expression. Phenotypic differences between double-mutant and GHD males suggest that lactogens and GH exert differential but overlapping effects on fat deposition and adipocytokine secretion and action.

Regulation of adiponectin receptor gene expression in diabetic mice

Adiponectin is an adipocyte-derived factor that plays pivotal roles in lipid and glucose metabolism in muscle and liver. The following two adiponectin receptor types were recently identified: AdipoR1 is abundantly expressed in muscle, whereas AdipoR2 is predominantly expressed in the liver. To clarify the regulation of adiponectin receptor gene expression in diabetic states, we examined mRNA levels of AdipoR1 in the muscles of diabetic animals by Northern blotting. The level of AdipoR1 mRNA was increased approximately 2.5-fold in muscle of streptozotocin (STZ) diabetic mice, but the normal level was restored by insulin administration, indicating that insulin has an inhibitory effect on AdipoR1 expression. To confirm this inhibitory effect of insulin, we performed in vitro experiments using C2C12 skeletal muscle cells. Insulin treatment for 24 h decreased AdipoR1 expression by approximately 60% in C2C12 cells. In addition, this effect was mediated by the phosphatidylinositol 3-kinase-dependent pathway rather than the mitogen-activated protein kinase pathway. AdipoR1 expression in insulin-resistant diabetic mice was also investigated. AdipoR1 expression was decreased by 36% in type 2 diabetic obese db/db mice compared with lean mice. In contrast, hepatic AdipoR2 expression was not significantly changed in either STZ mice or genetically obese mice. Our results indicate that regulation of AdipoR1, but not that of AdipoR2, may be involved in glucose and lipid metabolism in diabetic states.