Signaling

De Souza Goncalves B et al. 2026. Na/K-ATPase alpha1 subunit in adipocytes activates Src-family kinases to drive oxidative stress and pro-inflammatory signaling; NaKtide peptide inhibitor reduces systemic oxidative stress and atherosclerotic burden in vivo. Links fat-cell NKA signaling to cardiovascular disease independently of lipid metabolism.

Barbosa R et al. 2026. Visceral adipocytes overproduce endocannabinoids (2-AG, AEA) in obesity; this autocrine/paracrine signal drives adipocyte dysfunction and systemic insulin resistance via CB1 receptor activation.

Zhong X et al. 2026. Lipotoxic adipocytes package ANGPTL2 into exosomes that deliver ER stress to pancreatic beta cells via EIF2alpha/ATF4/CHOP; blocking exosome release or ANGPTL2 restores beta cell function in obese mice.

Genchi VA et al. 2026. Subcutaneous and visceral adipose progenitors differ in insulin receptor (IR) isoform expression during differentiation; IRb rises in subcutaneous while IRa predominates in visceral, linking depot identity to insulin signaling quality.

McTavish PV et al. 2026. DHA raises ANGPTL4 (an LPL inhibitor) in adipocytes via PPARgamma activation, reducing local LPL activity and diverting circulating triglycerides away from fat; a mechanism for omega-3 triacylglycerol lowering at the adipocyte level.

Oya M et al. 2026. Adipocyte-specific AM knockout mice fed HFD developed higher systolic blood pressure than controls; circulating AM was lower and renal dopaminergic responses were blunted. The fat cell secretes adrenomedullin that buffers hypertension during chronic metabolic stress -- another adipokine axis the kidney depends on.

Curtin MC, Jackson AE et al. 2026. Lean mammary adipocytes secrete 9S-HODE, an oxylipin that induces ferroptosis in breast cancer cells by disrupting iron homeostasis; obesity suppresses this secretion. The fat cell as tumor suppressor when healthy -- mechanism is iron-dependent lipid peroxidation, not immune recruitment.

Zhang et al. 1994. Leptin identified as the ob gene product, a 16-kDa adipocyte-secreted hormone that acts centrally via the hypothalamus to suppress appetite and regulate energy expenditure.

Scherer et al. 1995. Adiponectin (Acrp30) discovered as a second major adipokine, induced 100-fold during adipocyte differentiation, now known to improve insulin sensitivity via AdipoR1/R2.

Wu et al. 2012. Cold and beta-adrenergic stimulation recruit UCP1-positive beige adipocytes in white depots via a distinct developmental pathway from classical brown fat.

Summers 2006. Excess saturated fatty acids generate ceramide, which activates PP2A and PKCzeta to block Akt membrane translocation, impairing insulin signaling in adipocytes.

Leptolin identified as a novel adipokine positively correlated with exercise and inversely with BMI; it boosts energy expenditure in animal models, a candidate add to the adipokine output panel.

Curated review collection on adipokine biology and signaling, useful as a current overview of which adipokines are considered established versus candidate.

Reviews macrophage heterogeneity in adipose tissue: M1/M2 simplification is inadequate; single-cell data reveal multiple activation states with distinct metabolic roles.

Kitto ES et al. 2026. snRNA-seq and spatial transcriptomics reveal previously unappreciated adipocyte subpopulations across depots and disease states; cross-species comparisons clarify conserved vs. human-specific subsets.

Efthymiou V et al. 2026. snRNA-seq of human WAT identifies adipocyte subpopulations; a low-maturation subset linked to TSHZ3-mediated transcriptional suppression is associated with metabolic disease severity.

Grothen JER et al. 2026. NPY receptor 1 (NPY1R) identified as a cell-autonomous brake on adipocyte lipolysis; expression is inversely correlated with BMI and rises after weight loss, implicating neuropeptide Y signaling in direct lipolysis control.

Sahin C et al. 2026. Heterogeneous adipose progenitor subsets are characterized; specific subpopulations are required for thermogenic adipocyte generation and healthy remodeling, with implications for browning strategies.

Gual P et al. 2005. Review of the serine phosphorylation sites on IRS-1 that block insulin receptor interaction, including the TNF/JNK1 and ceramide pathways. [removed fabricated PNAS DOI; replaced with verified PMID]

Sano et al. 2003. The molecular step between Akt activation and GLUT4 appearance at the plasma membrane in adipocytes, completing the insulin-signaling cascade to glucose uptake.

Yamauchi et al. 2002. Mechanism by which adiponectin, the adipocyte-derived insulin sensitizer, acts on its target organs; explains why its loss in obesity worsens metabolic control.

Kitamura T et al. 1999. Insulin's anti-lipolytic action in adipocytes traced to PDE3B activation downstream of Akt, lowering cAMP and inactivating PKA and HSL.

Hotamisligil et al. 1993. Adipose tissue secretes TNF-alpha in obesity; it serine-phosphorylates IRS-1 via JNK1, blocking insulin receptor interaction. The founding paper on fat as an inflammatory organ.

Nicholls 1976. UCP1 mechanism established: purine nucleotides inhibit inner membrane conductance; long-chain fatty acids relieve this inhibition and drive proton leak as heat. The founding UCP1 paper.