Fat-specific protein 27α inhibits autophagy-dependent lipid droplet breakdown in white adipocytes.

AIMS/INTRODUCTION: Fat-specific protein 27 (FSP27) α is the major isoform of FSP27 in white adipose tissue (WAT), and is essential for large unilocular lipid droplet (LD) formation in white adipocytes. In contrast, FSP27ß is abundantly expressed in brown adipose tissue (BAT), and plays an important role in small multilocular LD formation. In FSP27 KO mice in which FSP27α and ß are both depleted, WAT is characterized by multilocular LD formation, and by increased mitochondrial abundance and energy expenditure, whereas BAT conversely manifests large oligolocular LDs and reduced energy expenditure. MATERIALS AND METHODS: We investigated the effects of autophagy in WAT and BAT of wild type (WT) and FSP27 knockout (KO) mice. In addition, we examined the effects of FSP27α and FSP27ß to the induction of autophagy in COS cells. RESULTS: Food deprivation induced autophagy in BAT of WT mice, as well as in WAT of FSP27 KO mice, suggesting that enhanced autophagy is characteristic of adipocytes with small multilocular LDs. Pharmacological inhibition of autophagy attenuated the fasting-induced loss of LD area in adipocytes with small multilocular LDs (BAT of WT mice and WAT of FSP27 KO mice), without affecting that in adipocytes with large unilocular or oligolocular LDs (WAT of WT mice or in BAT of FSP27 KO mice). Overexpression of FSP27α inhibited autophagy induction by serum deprivation in COS cells, whereas that of FSP27ß had no such effect. CONCLUSIONS: The present results thus showed that FSP27α inhibits autophagy and might thereby contribute to the energy-storage function of WAT.

Evaluation of metabolic parameters and body composition in Japanese patients with type 2 diabetes mellitus who were administered tofogliflozin for 48 weeks.

Sodium glucose cotransporter 2 inhibitors are unique antihyperglycemic agents that cause osmotic diuresis and calorie loss to urine. We previously reported that administration of tofogliflozin, a sodium glucose cotransporter 2 inhibitor, for 8 weeks decreased fat-free mass without affecting fat mass. We thus investigated the impact of tofogliflozin on metabolic parameters and body composition for 48 weeks in Japanese patients with type 2 diabetes mellitus. This single-arm open-label study enrolled 20 patients. Patients received tofogliflozin 20 mg once daily for 48 weeks. At week 48, changes in metabolic parameters and body composition from baseline were evaluated. Two patients discontinued administration due to adverse events during the first 8 weeks; however, no other adverse events occurred after that period. Seventeen patients completed the 48 weeks of administration of tofogliflodin. Body weight and body mass index decreased during the treatment period. Hemoglobin A1c decreased from 7.8% to 7.1%. The degree of improvement in hemoglobin A1c was correlated with body mass index, fat mass, and plasma glucose level at baseline. As for body composition, fat mass decreased without any change in fat-free mass (including total body water, extracellular water, and intracellular water). Red blood cell count and hematocrit increased, while the estimated glomerular filtration rate decreased. ALT and γ-GTP decreased and the decrease in γ-GTP was correlated with the loss of fat mass. In conclusion, our study clearly suggests that the body weight reduction caused by tofogliflozin administration for 48 weeks was almost entirely due to fat mass dissipation.

Impact of the 8-week Administration of Tofogliflozin for Glycemic Control and Body Composition in Japanese Patients with Type 2 Diabetes Mellitus.

Objective The adverse effects of selective sodium-glucose co-transporter 2 (SGLT2) inhibitors generally appear within about two or three months after treatment initiation in Japan. Therefore, we investigated the impact of tofogliflozin, a class of SGLT2 inhibitors, on glycemic control and body composition during this period in Japanese patients with type 2 diabetes mellitus. Methods This single-arm open-label study enrolled 20 patients. Patients received tofogliflozin 20 mg once daily for 8 weeks. At week 8, changes from baseline in body weight, serum metabolic markers, and body composition were evaluated. Results A total of 17 patients completed the 8-week administration of tofogliflodin. No serious adverse events were noted. Hemoglobin A1c (HbA1c) decreased significantly, from 7.8% to 7.3% with 8-week administration of tofogliflozin. Both the body weight and body mass index (BMI) also decreased. In addition, a decreased renal function of the boundary zone and hemoconcentration were detected. As for body composition, the free fat mass, total body water, extracellular water and intracellular water were all decreased significantly. Interestingly, the amount of fat mass did not change. The degree of improvement in HbA1c was correlated with the baseline fat mass and BMI. Conclusion An eight-week administration of tofogliflozin improved glycemic control and reduced the body weight and free fat mass in type 2 diabetic patients without affecting the fat mass. In this period, the hematocrit level and renal function should be monitored to guard against hemoconcentration and renal impairment, respectively.

Concurrent Therapy with a Low-carbohydrate Diet and Miglitol Remarkably Improved the Postprandial Blood Glucose and Insulin Levels in a Patient with Reactive Hypoglycemia due to Late Dumping Syndrome.

Reactive hypoglycemia induced by late dumping syndrome is often observed after gastrectomy. However, no effective therapy has yet been fully established. We herein describe a case in which concurrent therapy with a low-carbohydrate diet using low-glycemic-index food and an alpha-glucosidase inhibitor, miglitol, very effectively ameliorated the postprandial fluctuations in the blood glucose and plasma insulin levels in a patient with reactive hypoglycemia due to late dumping syndrome following total gastrectomy. The administration of miglitol under a low-carbohydrate diet using low-glycemic-index food may therefore be an ideal treatment for reactive hypoglycemia due to late dumping syndrome.

Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism.

OBJECTIVE: Although it has been recommended that serum free thyroxine (FT4) levels should be targeted to middle-upper normal levels during levothyroxine (l-T4) replacement therapy in patients with central hypothyroidism (CeH), the rationale has not been clarified. METHODS: A retrospective single-center study enrolled 116 patients with hypothyroidism (CeH, n=32; total thyroidectomy (Tx), n=22; primary hypothyroidism (PH), n=33; and control benign thyroid nodule (C), n=29). The patients had received L-T4 therapy at the Kobe University Hospital between 2003 and 2013. They were stratified according to serum FT4 level (≥ 1.10 or <1.10 ng/dl), and body temperature (BT), serum free triiodothyronine (FT3) levels, FT3/FT4 ratio, and lipid profiles were compared. The effect of GH replacement therapy on thyroid function was also analyzed. RESULTS: FT3 levels and FT3/FT4 ratios were significantly lower in patients with CeH than in patients with PH (P<0.05) or C (P<0.05). In patients with FT4 <1.10 ng/dl, BT was significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in patients with PH, whereas no differences were found in patients with FT4 ≥ 1.10 ng/dl. In patients with CeH, FT3 levels were higher in those with GH replacement therapy (P=0.018). CONCLUSION: In CeH, patients with median-lower normal levels of serum FT4 exhibited lower serum FT3 levels and lower BT. These results support the target levels of serum FT4 as middle-upper normal levels during l-T4 replacement therapy in patients with CeH.