Brain-to-BAT - and Back?: Crosstalk between the Central Nervous System and Thermogenic Adipose Tissue in Development and Therapy of Obesity

Figures

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  Figure 1. Brown Adipose Tissue (BAT) localization, architecture and role in thermogenesis. ATGL, adipose triglyceride lipase; fFAs, free fatty acids; GLUT, Glucose transporter; HSL, hormone-sensitive lipase; NE norepinephrine, PKA, protein kinase A, TG, triglycerides.

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  Figure 2. Multifaceted regulation of BAT activity. Thermogenic activity in brown adipose tissue (BAT) is controlled in response to cold exposure or caloric excess via various control mechanisms. These include the Sympathetic Nervous System (SNS) originating within the hypothalamus, crosstalk with White Adipose Tissue (WAT), modulation by thyroid hormones, transcriptional regulation by the circadian rhythm and input from liver, muscles and gastrointestinal tract (GIT). The latter mechanism can be mediated either directly via the secretion of gut hormones such as secretin by GIT cells or by alterations in the gut microbiome and subsequent changes in microbial metabolite profiles within the GIT or the circulation (with long-ranging effects on the entire body). Neuronal signaling routes are displayed in red, and molecules exerting signaling effects are shown in blue. BAs, bile acids, BCAA, branch-chained amino acids; GCG, Glucagon; GIP, gastric inhibitory peptide; GLP-1 Glucagon-like protein-1; HyT, hypothalamus; NE, norepinephrine; SCFA, short-chained fatty acids; secBA, secondary bile acids; SNS, sympathetic nervous system; PG, pituitary gland.

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  Figure 3. Neural circuitry controlling BAT activity. Major neuronal signaling routes are displayed in red, and molecules exerting signaling effects are shown in blue. β3AR, β3 adrenergic receptor; AdR, adenosine receptor(s); BAT, brown adipose tissue; DMH, dorsomedial hypothalamus; ECs, Endocannabinoids; GIT, gastrointestinal tract; HyT, hypothalamus; IML, intermediolateral nucleus; LHA, lateral hypothalamic area; MCs, Melanocortins; NE, norepinephrine; PG, pituitary gland; POA, preoptic area; Rp, Raphe pallidus; SNS, sympathetic nervous system; VMH, ventromedial hypothalamus; WAT, white adipose tissue.