Smooth muscle cell-derived Cxcl12 directs macrophage accrual and sympathetic innervation to control thermogenic adipose tissue.

Sympathetic innervation of brown adipose tissue (BAT) controls mammalian adaptative thermogenesis. However, the cellular and molecular underpinnings contributing to BAT innervation remain poorly defined. Here, we show that smooth muscle cells (SMCs) support BAT growth, lipid utilization, and thermogenic plasticity. Moreover, we find that BAT SMCs express and control the bioavailability of Cxcl12. SMC deletion of Cxcl12 fosters brown adipocyte lipid accumulation, reduces energy expenditure, and increases susceptibility to diet-induced metabolic dysfunction. Mechanistically, we find that Cxcl12 stimulates CD301+ macrophage recruitment and supports sympathetic neuronal maintenance. Administering recombinant Cxcl12 to obese mice or leptin-deficient (Ob/Ob) mice is sufficient to boost macrophage presence and drive sympathetic innervation to restore BAT morphology and thermogenic responses. Altogether, our data reveal an SMC chemokine-dependent pathway linking immunological infiltration and sympathetic innervation as a rheostat for BAT maintenance and thermogenesis.

Age-dependent Pdgfrß signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice.

Perivascular adipocyte progenitor cells (APCs) can generate cold temperature-induced thermogenic beige adipocytes within white adipose tissue (WAT), an effect that could counteract excess fat mass and metabolic pathologies. Yet, the ability to generate beige adipocytes declines with age, creating a key challenge for their therapeutic potential. Here we show that ageing beige APCs overexpress platelet derived growth factor receptor beta (Pdgfrß) to prevent beige adipogenesis. We show that genetically deleting Pdgfrß, in adult male mice, restores beige adipocyte generation whereas activating Pdgfrß in juvenile mice blocks beige fat formation. Mechanistically, we find that Stat1 phosphorylation mediates Pdgfrß beige APC signaling to suppress IL-33 induction, which dampens immunological genes such as IL-13 and IL-5. Moreover, pharmacologically targeting Pdgfrß signaling restores beige adipocyte development by rejuvenating the immunological niche. Thus, targeting Pdgfrß signaling could be a strategy to restore WAT immune cell function to stimulate beige fat in adult mammals.

The Regulation of Adipose Tissue Health by Estrogens.

Obesity and its' associated metabolic diseases such as type 2 diabetes and cardiometabolic disorders are significant health problems confronting many countries. A major driver for developing obesity and metabolic dysfunction is the uncontrolled expansion of white adipose tissue (WAT). Specifically, the pathophysiological expansion of visceral WAT is often associated with metabolic dysfunction due to changes in adipokine secretion profiles, reduced vascularization, increased fibrosis, and enrichment of pro-inflammatory immune cells. A critical determinate of body fat distribution and WAT health is the sex steroid estrogen. The bioavailability of estrogen appears to favor metabolically healthy subcutaneous fat over visceral fat growth while protecting against changes in metabolic dysfunction. Our review will focus on the role of estrogen on body fat partitioning, WAT homeostasis, adipogenesis, adipocyte progenitor cell (APC) function, and thermogenesis to control WAT health and systemic metabolism.

Encapsulation of Lutein in Nanoemulsions Stabilized by Resveratrol and Maillard Conjugates.

Lutein is incorporated into foods as a natural yellow pigment and nutraceutical. The introduction of lutein into many foods and beverages, however, is problematic because of its strong hydrophobicity and poor chemical stability. In this research, lutein-loaded nanoemulsions were prepared to overcome this problem. Casein-dextran Maillard conjugates or physical complexes were utilized as emulsifiers, while either medium chain triglycerides (MCT) or grape seed oil (GSO) were used as carrier oils. The impact of resveratrol addition on nanoemulsion stability was also examined. The influence of storage temperature, pH, and CaCl2 concentration on the chemical and physical stability of the nanoemulsions was measured. The casein-dextran conjugates were highly effective at improving the physical resistance of the nanoemulsions to environmental stresses, but had a detrimental effect on their color stability. Conversely, nanoemulsions prepared from casein-dextran physical complexes were unstable around the protein's isoelectric point (pH 4.6), as well as upon addition of CaCl2 . Incorporation of resveratrol and GSO into the nanoemulsions decreased lutein degradation and color fading at all temperatures. This study shows that casein-dextran conjugates are highly effective at improving the physical stability of lutein-loaded nanoemulsions, while resveratrol and GSO are effective at improving their chemical stability. PRACTICAL APPLICATION: Lutein can be used by the food industry to create "clean label" and functional food products. The major challenges in incorporating lutein in foods are its poor chemical stability and its high hydrophobicity, which makes it difficult to incorporate. Emulsion-based delivery systems assembled from natural ingredients may address these challenges. In this study, the impact of Maillard conjugates fabricated from caseinate and dextran, as well as resveratrol addition, on the formation and stability of lutein-enriched nanoemulsions was determined. The information obtained from this study will help the formulation of more effective functional foods and beverage products.