CNS targets of adipokines

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Our understanding of adipose tissue as an endocrine organ has been transformed over the last twenty years. During this time a number of adipocyte-derived factors or adipokines have been identified. This paper will review evidence for how adipokines acting via the central nervous system (CNS) regulate normal physiology and disease pathology. The reported CNS-mediated effects of adipokines are varied and include the regulation of energy homeostasis, autonomic nervous system activity, the reproductive axis, neurodevelopment, cardiovascular function, and cognition. Due to the wealth of information available and the diversity of their known functions, the archetypal adipokines leptin and adiponectin will be the focused on extensively. Other adipokines with established CNS actions will also be discussed. Due to the difficulties associated with studying CNS function on a molecular level in humans, the majority of our knowledge, and as such the studies described in this paper, comes from work in experimental animal models; however, where possible the relevant data from human studies are also highlighted

Mechanism of muscle atrophy in a normal-weight rat model of type 2 diabetes established by using a soft-pellet diet

Abstract Dietary factors such as food texture affect feeding behavior and energy metabolism, potentially causing obesity and type 2 diabetes. We previously found that rats fed soft pellets (SPs) were neither hyperphagic nor overweight but demonstrated glucose intolerance, insulin resistance, and hyperplasia of pancreatic β-cells. In the present study, we investigated the mechanism of muscle atrophy in rats that had been fed SPs on a 3-h time-restricted feeding schedule for 24 weeks. As expected, the SP rats were normal weight; however, they developed insulin resistance, glucose intolerance, and fat accumulation. In addition, skeletal muscles of SP rats were histologically atrophic and demonstrated disrupted insulin signaling. Furthermore, we learned that the muscle atrophy of the SP rats developed via the IL-6–STAT3–SOCS3 and ubiquitin–proteasome pathways. Our data show that the dietary habit of consuming soft foods can lead to not only glucose intolerance or insulin resistance but also muscle atrophy

Cafeteria Diet Increased Adiposity In Comparison To High Fat Diet In Young Male Rats

Background Dietary intervention studies in animal models of obesity are crucial to elucidate the mechanistic effects of specific nutrients and diets. Although several models of diet induced obesity have been examined in rodents to assess obesity, there are few studies that have researched influence of different high fat and/or westernized diets. The aim of this study was to compare a high fat diet and a cafeteria diet on obesity related biochemical and physiological parameters in young male rats. Methods Five week old Wistar male rats were fed a control chow diet (C), butter-based high fat diet (HF) or cafeteria diet (CAF) for twelve weeks. In HF, 40% of energy came from fat and this ratio was 46% in CAF. CAF composed of highly energetic and palatable human foods along with chow diet. At the end of the feeding protocol all animals were culled using CO2 asphyxia and cervical dislocation after an overnight fasting. Results Total energy and fat intake of CAF was significantly higher than C and HF. CAF was more effective in inducing obesity, as demonstrated by increased weight gain, Lee index, fat depot weights and total body fat in comparison to C and HF. Despite increased adiposity in CAF, plasma glucose, insulin and HOMA-IR levels were similar between the groups. Plasma leptin and cholesterol levels were markedly higher in CAF than C and HF. Discussion We have demonstrated that there are differential effects of high fat diet and cafeteria diet upon obesity and obesity-related parameters, with CAF leading to a more pronounced adiposity in comparison to high fat diet in young male rats. Future studies should consider the varied outcomes of different diet induced obesity models and development of a standardized approach in similar research practices.PubMedWoSScopu

SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals

Background: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Methodology/Principal Findings: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)γ[subscript gamma] was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ[subscript gamma] and enhanced PIP5Kγ[subscript gamma] enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ[subscript gamma] knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P[subscript 2], and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ[subscript gamma] pathway is important for regulating the metabolism of the whole body.Mitsubishi Institute of Life SciencesJapan Society for the Promotion of Science. (WAKATE S grant