Obesity: Suzuki A

Suzuki A, Abdelmalek MF. · Division of Gastroenterology & Hepatology, Duke University Medical Center, Durham, NC 27710, USA. · Womens Health (Lond Engl). · Pubmed #19245356 No free full text.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed countries and is increasing in prevalence with the rise of diabetes and obesity. In addition to obesity and age, gender may also influence the prevalence and severity of NAFLD. However, mechanisms underlying gender-based differences in NAFLD have not been clearly defined. Furthermore, alterations in body composition, fat distribution and/or hormonal or metabolic changes that occur following menopause and in the setting of polycystic ovary syndrome may influence the development and progression of NAFLD. In this article, we will summarize known gender differences as well as the proposed mechanisms for gender differences in NAFLD, review two women-specific issues that may influence the prevalence and severity of NAFLD, menopause and polycystic ovary syndrome, and discuss potential therapeutic options for women with NAFLD who are postmenopausal or have polycystic ovary syndrome.

Obata R, Adachi Y, Igarashi H, Suzuki A, Obata Y, Doi M, Sato S. · Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu 431-3192. · Masui. · Pubmed #18975547 No free full text.

Abstract: We experienced anesthesia for a female patient of BMI 39.2 with unanticipated lingual tonsillar hyperplasia. At the induction of anesthesia, both mask ventilation and tracheal intubation were difficult due to the lingual tonsillar hyperplasia. However, tracheal intubation was performed by Intubating LMA with the fiberoptic bronchoscopy. After the placing of TE (the catheter for tracheal tube exchanger), the tracheal tube was extubated without any airway trouble. Following the extubation, the opening of the respiratory tract was evaluated by TE and the fiberoptic bronchoscopy. In this case we confirmed that the ASA difficult airway algorithm was also useful in the presence of lingual tonsillar hyperplasia.

Oda N, Imamura S, Fujita T, Uchida Y, Inagaki K, Kakizawa H, Hayakawa N, Suzuki A, Takeda J, Horikawa Y, Itoh M. · Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. · Metabolism. · Pubmed #18191059 No free full text.

Abstract: The level of leptin increases with obesity, whereas that of adiponectin decreases with obesity. It is reported that the ratio of leptin to adiponectin (L/A) is associated with insulin resistance. It is difficult to evaluate insulin resistance in diabetic patients who have a dysfunction of insulin secretion. The aim of this study was to examine whether the L/A ratio is a useful marker for insulin resistance in diabetic patients. We examined L/A in the serum of a total of 139 Japanese patients with type 2 diabetes mellitus (66 women and 73 men) and 7 healthy individuals recruited in our hospital. Changes in the levels of leptin and adiponectin were observed using the oral glucose tolerance test and a hyper- and euglycemic clamp test. Twenty-one patients with type 2 diabetes mellitus were observed for more than 6 months after treatment with pioglitazone, and 31 patients with type 2 diabetes mellitus were observed for more than 6 months after the treatment with metformin. The mean value of L/A in 139 Japanese patients with type 2 diabetes mellitus was 1.22 +/- 1.41 (1.68 +/- 1.76 in women, 0.81 +/- 0.80 in men; P = .0002). In the clamp tests, L/A correlated with glucose infusion rate (GIR) (r(2) = 0.26, P = .0034). The correlation of L/A and GIR indicated a stronger correlation than either leptin (r(2) = 0.144, P = .03) or adiponectin alone (r(2) = 0.023, P = .41), or the homeostasis model assessment of insulin resistance (r(2) = 0.103, P = .08). The average hemoglobin A(1c) (HbA(1c)) improved from 10.2% +/- 1.2% to 9.2% +/- 1.6% (P = .0037) in 6 months after treatment with pioglitazone. Our results indicate pioglitazone to be effective for HbA(1c) improvement in subjects with high L/A and low L/A. The average HbA(1c) improved from 9.2% +/- 0.9% to 8.0% +/- 1.2% (P = .0002) in 6 months after treatment with metformin. Our results indicate metformin to be effective for HbA(1c) improvement in subjects with a low L/A. In conclusion, we demonstrate that L/A is different between male and female subjects. The correlation of L/A and GIR by the euglycemic hyperinsulinemic clamp test suggests that L/A is a useful indicator for the choice of drug to treat diabetes mellitus.

Patten CS, Daniels D, Suzuki A, Fluharty SJ, Yee DK. · Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St. 220E, Philadelphia, PA 19104, USA. · Regul Pept. · Pubmed #17376547 No free full text.

Abstract: In addition to its well known stimulation of cAMP production, the human melanocortin type 4 (hMC4) receptor recently has been shown to mediate p44/42 MAPK activation. This finding opens new questions about the structural and signaling mechanisms that connect the receptor to this alternate cell signaling pathway. Point mutants in the hMC4 receptor that have been associated with obesity were constructed and transfected into HEK 293 cells. Functional analyses then were done to determine if these mutations would similarly impact cAMP formation and p44/42 MAPK signaling. Whereas a D90N mutation in the second transmembrane domain and a D298A mutation in the seventh transmembrane domain impaired both cAMP formation and p44/42 MAPK activation, a more conservative D298N mutation retained cAMP formation but abolished p44/42 MAPK activation. The D298N mutation identified, for the first time, differential structural requirements of the hMC4 receptor for activation of the cAMP and p44/42 MAPK pathways. Furthermore, functional characterizations of a series of chimeric receptors combining the hMC4 receptor and the hMC3 subtype, a receptor that does not couple to p44/42 MAPK activation despite stimulating adenylyl cyclase, indicate that the hMC4 cytoplasmic tail is a necessary structural element for p44/42 MAPK signaling. Subsequent investigation of the signaling requirements for p44/42 MAPK activation demonstrated that the adenylyl cyclase inhibitor 2', 5'-dideoxyadenosine blocked agonist-induced p44/42 MAPK activation, but the PKA inhibitor Rp cAMPS did not. Taken together, these data indicate that cAMP is required, but not sufficient for p44/42 MAPK activation and suggest structural elements required for hMC4 receptor signaling.

Inagaki K, Suzuki A, Nagata M, Sekiguchi S, Itoi T, Asano S, Hiroaki K, Hayakawa N, Oda N, Itoh M. · Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University, Toyoake. · Nippon Naika Gakkai Zasshi. · Pubmed #17240887 No free full text.

This publication has no abstract.

Yoshida I, Suzuki A, Vallée M, Matano Y, Masunaga T, Zenda T, Shinozaki K, Okada T. · Second Department of Internal Medicine, Kanazawa University [corrected] and Hokuriku Hospital, Kanazawa, Ishikawa, Japan. · Clin Gastroenterol Hepatol. · Pubmed #16979948 No free full text.

Abstract: BACKGROUND & AIMS: Obesity and diabetes mellitus are associated with an increased incidence of proximal colon cancer. Colonic adenoma that has been reported to be associated with elevated serum insulin levels and subsets of hyperplastic polyps might serve as a precursor of colon cancer. In this study, we sought to determine segment-specific associations between serum insulin levels and the prevalence of adenoma and hyperplastic polyps in the proximal and distal colon. METHODS: We studied 343 consecutive patients who underwent colonoscopy in our hospital. All medical information, including fasting serum insulin, was obtained at colonoscopy. We performed multinomial logistic regression models by using the outcome categories of none (reference), proximal-only, distal-only, and both-segment lesions for the presence of adenoma/hyperplastic polyp with serum insulin, age, gender, lifestyle characteristics, and the presence of other types of lesions as predictors. Odds ratios (ORs) and 95% confidence intervals (CIs) are provided for a 5-muU/mL increase in serum insulin. RESULTS: Overall, serum insulin levels were significantly associated with adenoma (OR, 1.5; 95% CI, 1.1-2.0; P = .005) and borderline associated with hyperplastic polyps (OR, 1.3; 95% CI, 1.0-1.7; P = .075). In multinomial logistic regression models, elevated serum insulin levels were significantly associated with proximal-only adenoma (OR, 1.8; 95% CI, 1.2-2.5; P = .002), both-side hyperplastic polyp (OR, 1.7; 95% CI, 1.1-2.5; P = .015), and proximal-only hyperplastic polyp (OR, 1.5; 95% CI, 1.0-2.1; P = .048) and borderline associated with distal-only adenoma (OR, 1.5; 95% CI, 1.0-2.1; P =.059) but not with distal-only hyperplastic polyp. CONCLUSIONS: Serum insulin levels directly correlate with the presence of adenoma and hyperplastic polyps in the proximal colon and might also less strongly correlate with the presence of distal adenoma.

Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, Ashcroft FM, Brüning JC. · Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne (CMMC), Cologne, Germany. · J Clin Invest. · Pubmed #16794735 links to  free full text

Abstract: Leptin and insulin have been identified as fuel sensors acting in part through their hypothalamic receptors to inhibit food intake and stimulate energy expenditure. As their intracellular signaling converges at the PI3K pathway, we directly addressed the role of phosphatidylinositol3,4,5-trisphosphate-mediated (PIP3-mediated) signals in hypothalamic proopiomelanocortin (POMC) neurons by inactivating the gene for the PIP3 phosphatase Pten specifically in this cell type. Here we show that POMC-specific disruption of Pten resulted in hyperphagia and sexually dimorphic diet-sensitive obesity. Although leptin potently stimulated Stat3 phosphorylation in POMC neurons of POMC cell-restricted Pten knockout (PPKO) mice, it failed to significantly inhibit food intake in vivo. POMC neurons of PPKO mice showed a marked hyperpolarization and a reduction in basal firing rate due to increased ATP-sensitive potassium (KATP) channel activity. Leptin was not able to elicit electrical activity in PPKO POMC neurons, but application of the PI3K inhibitor LY294002 and the KATP blocker tolbutamide restored electrical activity and leptin-evoked firing of POMC neurons in these mice. Moreover, icv administration of tolbutamide abolished hyperphagia in PPKO mice. These data indicate that PIP3-mediated signals are critical regulators of the melanocortin system via modulation of KATP channels.

Kosuge K, Sasaki H, Ikarashi T, Toyabe S, Akazawa K, Kobayashi C, Abe E, Suzuki A, Saito H, Eguchi S, Otsuka H, Aizawa Y. · Diabetes Center, Niigata-Kobari Hospital, Niigata, Japan. · J Atheroscler Thromb. · Pubmed #16505593 links to  free full text

Abstract: To investigate risk factors for coronary artery disease (CAD), we analyzed the clinical parameters of patients with a coronary artery bypass graft (CABG) in a case-control study. Eighty-eight patients (75 males and 13 females) who underwent CABG surgery between 2001 and 2002 were compared with age- and sex-matched healthy controls randomly chosen from the registry of Kobari Health Care Center. Wilcoxon's signed rank test and McNemar's test were used for pairwise comparisons. Multivariate logistic regression analysis was used to identify significant risk factors for CABG. Significant differences between the patients and controls were observed in HDL-C (p < 0.001), HbA(1c) (p < 0.001), Brinkman Index (BI; p < 0.001), body mass index (BMI; p = 0.002), and systolic blood pressure (SBP; p = 0.013). Subjects with an abnormal BMI, HbA(1c), or HDL-C or high BI value made up a significantly higher proportion of the patients who underwent CABG, compared to their age- and sex-matched controls. Multivariate logistic regression analysis identified high levels of HbA(1c), low levels of HDL-C, and high scores on the BI as significant risk factors for needing a CABG. These results demonstrate that, despite the modification of laboratory determinations by antecedent treatment, HDL-C, HbA(1c), BI, BMI, and SBP are significant indicators of risk for CAD.

Suzuki A, Terao M, Fujita S, Henderson JJ. · No affiliation provided · Anaesthesia. · Pubmed #18336505 No free full text.

This publication has no abstract.

Komazawa N, Matsuda M, Kondoh G, Mizunoya W, Iwaki M, Takagi T, Sumikawa Y, Inoue K, Suzuki A, Mak TW, Nakano T, Fushiki T, Takeda J, Shimomura I. · Department of Social and Environmental Medicine, Graduate School of Frontier Bioscience, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan. · Nat Med. · Pubmed #15489860 No free full text.

Abstract: Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enhanced insulin sensitivity with induced phosphorylation of Akt in adipose tissue. AdipoPten-KO mice also showed marked hyperthermia and increased energy expenditure with induced mitochondriagenesis in adipose tissue, associated with marked reduction of p53, inactivation of Rb, phosphorylation of cyclic AMP response element binding protein (CREB) and increased expression of Ppargc1a, the gene that encodes peroxisome proliferative activated receptor gamma coactivator 1 alpha. Physiologically, adipose Pten mRNA decreased with exposure to cold and increased with obesity, which were linked to the mRNA alterations of mitochondriagenesis. Our results suggest that altered expression of adipose Pten could regulate insulin sensitivity and energy expenditure. Suppression of adipose Pten may become a beneficial strategy to treat type 2 diabetes and obesity.