Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.oth white adipose tissue (WAT) and brown adipose tissue (BAT) function in the energy homeostasis of humans and other mammals. WAT stores energy in form of triglycerides during periods of excessive caloric intake for later use when energy demand exceeds intake (1). In contrast, brown adipose tissue (BAT) uses "stored triglycerides" to generate energy in the form of heat, most notably when environmental temperature falls (2).The excessive accumulation of body fat in WAT is the result of both hypertrophy and hyperplasia of white adipocytes (3). Such changes give rise to insulin resistance, type-2 diabetes, and an inflammatory response, thus implicating white adipocytes in the etiology of these conditions (4, 5). In contrast, promotion of BAT activities helps prevent genetic obesity, insulin resistance, and diabetes (6).Unlike the expansive mass of brown adipocytes in the interscapular region, brown adipose tissue mass in the normal adult human is proportionally smaller and previously was believed to be functionally less important. Recently, however, by using [18F]-2-fluoro-D-2-deoxy-D-glucose PET, metabolically active regions were detected in the cervical, supraclavicular, axillary, and paravertebral regions of adult human subjects (7-9). The metabolically active areas were found to consist of an admixture of brown-like adipocytes in WAT (10) which increase dramatically following cold exposure or treatment with antidiabetic drugs, thiazolidinediones, or adrenergic activators (11-13). These cells recently have been designated as "beige" (14) or "brite" (15, 16) cells derived from ...

Brown adipose tissue (BAT) is an energy-expending organ that produces heat. Expansion or activation of BAT prevents obesity and diabetes. Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1 (UCP1) activation triggered via a β-adrenergic pathway. Here, we report that the cold-sensing transient receptor potential melastatin 8 (TRPM8) is functionally present in mouse BAT. Challenging brown adipocytes with menthol, a TRPM8 agonist, up-regulates UCP1 expression and requires protein kinase A activation. Upon mimicking long-term cold exposure with chronic dietary menthol application, menthol significantly increased the core temperatures and locomotor activity in wild-type mice; these effects were absent in both TRPM8(-/-) and UCP1(-/-) mice. Dietary obesity and glucose abnormalities were also prevented by menthol treatment. Our results reveal a previously unrecognized role for TRPM8, suggesting that stimulation of this channel mediates BAT thermogenesis, which could constitute a promising way to treat obesity.

Oral biofilms attach onto both teeth surfaces and dental material surfaces in oral cavities. In the meantime, oral biofilms are not only the pathogenesis of dental caries and periodontitis, but also secondary caries and peri-implantitis, which would lead to the failure of clinical treatments. The material surfaces exposed to oral conditions can influence pellicle coating, initial bacterial adhesion, and biofilm formation, due to their specific physical and chemical characteristics. To define the effect of physical and chemical characteristics of dental prosthesis and restorative material on oral biofilms, we discuss resin-based composites, glass ionomer cements, amalgams, dental alloys, ceramic, and dental implant material surface properties. In conclusion, each particular chemical composition (organic matrix, inorganic filler, fluoride, and various metallic ions) can enhance or inhibit biofilm formation. Irregular topography and rough surfaces provide favorable interface for bacterial colonization, protecting bacteria against shear forces during their initial reversible binding and biofilm formation. Moreover, the surface free energy, hydrophobicity, and surface-coating techniques, also have a significant influence on oral biofilms. However, controversies still exist in the current research for the different methods and models applied. In addition, more in situ studies are needed to clarify the role and mechanism of each surface parameter on oral biofilm development.

High sodium intake is a major risk factor for developing hypertension in diabetes. Promotion of sodium excretion reduces cardiometabolic lesions in diabetes. However, the interaction between sodium intake and glucose homeostasis remains elusive. Here, we report that high sodium intake remarkably increased natriuresis in wild-type mice, but this effect was blunted in adipose-specific PPARδ knockout mice and diabetic mice. PPARδ activation in perirenal fat by agonist or high sodium intake inhibited renal sodium-glucose cotransporter 2 (SGLT2) function, which is mediated by increased production of adipose adiponectin. In addition, high salt intake-induced natriuresis was impaired in diabetic states because of renal SGLT2 dysfunction. Type 2 diabetic patients with uncontrolled hyperglycemia had less natriuresis that was correlated to their plasma adiponectin levels. Our findings provide insights into the distinctive role of the PPARδ/adiponectin/SGLT2 pathway in the regulation of sodium and glucose homeostasis.