Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.
Acetyl-CoA Carboxylase ; Animals ; Betaine ; Brain ; Carnitine O-Palmitoyltransferase ; Catalase ; Diet ; Diet, High-Fat ; Endoplasmic Reticulum ; Gluconeogenesis ; Glucose ; Glutathione ; Humans ; Hyperinsulinism ; Hyperlipidemias ; Insulin Resistance ; JNK Mitogen-Activated Protein Kinases ; Lipid Metabolism ; Lipid Peroxidation ; Liver ; Male ; Mice ; Oxidative Stress ; PPAR alpha ; PPAR gamma ; RNA, Messenger ; Transcription Factors

Purpose: Latissimus dorsi mini-flap (LDMF) reconstruction after breast-conserving surgery (BCS) is a useful volume replacement technique when a large tumor is located in the upper or outer portion of the breast. However, few studies have reported the impact of LDMF on patients’ quality of life (QoL) and cosmesis compared with conventional BCS. Methods: We identified patients who underwent BCS with or without LDMF between 2010 and 2020 at a single center. At least 1 year after surgery, we prospectively administered the BREAST-Q to assess QoL and obtained the patients’ breast photographs. The cosmetic outcome was assessed using four panels composed of physicians and the BCCT.core software. Results: A total of 120 patients were enrolled, of whom 62 and 58 underwent LDMF or BCS only, respectively. The LDMF group had significantly larger tumors, shorter nipple-to-tumor distances in preoperative examinations, and larger resected breast volumes than did the BCSonly group (p < 0.001). The questionnaires revealed that QoL was poorer in the LDMF group, particularly in terms of the physical well-being score (40.9 vs. 20.1, p < 0.001). Notably, the level of patients’ cosmetic satisfaction with their breasts was comparable, and the cosmetic evaluation was assessed by panels and the BCCT.core software showed no differences between the groups. Conclusion Our results showed that cosmetic outcomes of performing LDMF are comparable to those of BCS alone while having the advantage of resecting larger volumes of breast tissue. Therefore, for those who strongly wish to preserve the cosmesis of their breasts, LDMF can be considered a favorable surgical option after the patient is oriented toward the potential for physical dysfunction after surgery.