About

Alan Saltiel is a Professor of Medicine at UC San Diego, specializing in endocrinology and metabolic research. His research activities focus on hormonal regulation of LDL receptor trafficking, energy expenditure in adipose tissue, inflammation and hepatic lipid metabolism, and adipose tissue plasticity in health and disease. He has contributed to understanding the molecular mechanisms underlying insulin action, glycogen metabolism, and thermogenic remodeling of white adipocytes. His work also explores the regulation of glucose homeostasis, mitochondrial dynamics in adipocytes, and the metabolic benefits of various signaling pathways. Saltiel's research is funded by multiple NIH grants, and he has made significant contributions to the field of metabolic biology through his investigations into obesity, diabetes, and related metabolic disorders.

Research topics

• Endocrinology
• Biology
• Biochemistry
• Internal medicine
• Medicine
• Chemistry
• Cell biology
• Cancer research
• Genetics
• Neuroscience
• Bioinformatics

Selected publications

• Protocol for differentiating murine 3T3-L1 and SVF-derived preadipocytes and isolating crude mitochondrial fractions

  STAR Protocols · 2025-08-23 · 1 citations

  articleOpen accessSenior authorCorresponding

  Here, we present a protocol for differentiating 3T3-L1 preadipocytes and stromal vascular fraction (SVF)-derived preadipocytes from mice into mature adipocytes, followed by the isolation of crude mitochondrial fractions. This cost-effective and reproducible protocol is optimized for small-plate formats, compatible with standard reagents, and suitable for metabolic studies such as insulin resistance and mitochondrial function. • Culture of mouse 3T3-L1 fibroblasts • Isolation of primary preadipocytes from mouse iWAT • Differentiation of mouse 3T3-L1 and SVF-derived preadipocytes into adipocytes • Isolation of crude mitochondrial and cytosolic fractions from mouse adipocytes Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Here, we present a protocol for differentiating 3T3-L1 preadipocytes and stromal vascular fraction (SVF)-derived preadipocytes from mice into mature adipocytes, followed by the isolation of crude mitochondrial fractions. This cost-effective and reproducible protocol is optimized for small-plate formats, compatible with standard reagents, and suitable for metabolic studies such as insulin resistance and mitochondrial function.

  PublisherDOI

• Multi-layered transcriptional control of glycogen metabolism coordinates thermogenic remodeling of white adipocytes in male mice

  Nature Communications · 2025-12-16 · 1 citations

  articleOpen accessSenior author

  Thermogenic activation of subcutaneous white adipocytes requires glycogen synthesis and turnover. Here we show that β-adrenergic stimulation induces a distinct glycogen metabolism gene program in inguinal white adipose tissue in a cell-autonomous and adipocyte-specific manner. Among these, Gys2 and Ppp1r3c are rapidly induced following acute β3-adrenergic receptor activation. We identify Gys2 as a direct transcriptional target of PKA-CREB signaling. In contrast, sustained expression of glycogen metabolism genes under chronic β3-adrenergic activation requires the coactivator PGC1α, whose loss blunts glycogen accumulation and thermogenic capacity. Mechanistically, PGC1α cooperates with estrogen-related receptors (ERRs) to regulate chromatin accessibility and gene transcription. Although deletion of ERRα is compensated by ERRγ, combined deletion of ERRα/β/γ abolishes expression of glycogen metabolism and thermogenic genes. Chromatin profiling confirm that ERRs directly control the glycogen metabolic program in beige adipocytes. Together, our results identify a multilayered transcriptional axis that sustains glycogen metabolism during β-adrenergic activation in male mice.

  PublisherOA PDFDOI

• Tank-Binding Kinase 1 protects against MASH progression via mitochondrial quality control

  Research Square · 2025-10-09

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• Neutrophils preserve energy storage in sympathetically activated adipocytes

  Nature · 2025-12-10 · 2 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Pedro Cuatrecasas (1936–2025)

  Nature Biotechnology · 2025-12-03

  article1st authorCorresponding
  PublisherDOI

• Sympathetic activation of white adipose tissue recruits neutrophils to limit energy expenditure

  Research Square · 2025-04-15 · 1 citations

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Hepatic glycogen directly regulates gluconeogenesis through an AMPK/CRTC2 axis in mice

  Journal of Clinical Investigation · 2025-06-01 · 10 citations

  articleOpen accessSenior author

  Glycogenolysis and gluconeogenesis ensure sufficient hepatic glucose production during energy shortages. Here, we report that hepatic glycogen levels control the phosphorylation of a transcriptional coactivator to determine the amplitude of gluconeogenesis. Decreased liver glycogen during fasting promotes gluconeogenic gene expression, while feeding-induced glycogen accumulation suppresses it. Liver-specific deletion of the glycogen scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels, increases the expression of gluconeogenic genes, and promotes glucose production in primary hepatocytes. In contrast, liver glycogen phosphorylase (PYGL) knockdown or inhibition increases glycogen levels and represses gluconeogenic gene expression. These changes in hepatic glycogen levels are sensed by AMP-activated protein kinase (AMPK). AMPK activity is increased when glycogen levels decline, resulting in the phosphorylation and stabilization of CREB-regulated transcriptional coactivator 2 (CRTC2), which is crucial for the full activation of the cAMP-responsive transcriptional factor CREB. High glycogen allosterically inhibits AMPK, leading to CRTC2 degradation and reduced CREB transcriptional activity. Hepatocytes with low glycogen levels or high AMPK activity show higher CRTC2 protein levels, priming the cell for gluconeogenesis through transcriptional regulation. Thus, glycogen plays a regulatory role in controlling hepatic glucose metabolism through the glycogen/AMPK/CRTC2 signaling axis, safeguarding efficient glucose output during fasting and suppressing it during feeding.

  PublisherDOI

• 1272 LUMINAL BILE SALT HYDROLASE ACTIVITY IMPROVES HOST GLUCOSE HOMEOSTASIS

  Gastroenterology · 2024-05-01

  article
  PublisherDOI

• TIME-RESTRICTED EATING PROMOTES WEIGHT LOSS AND REDUCTION IN BODY FAT VS STANDARD OF CARE: A RANDOMIZED CONTROL TRIAL IN INDIVIDUALS WITH OBESITY

  Journal of the American College of Cardiology · 2024-04-01

  article
  PublisherDOI

• Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation

  Nature Metabolism · 2024-01-29 · 134 citations

  articleOpen accessSenior author

  Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01DK076906

  NIH · $4.6M · 2020

• NIH Grant R21DK098776

  NIH · $415k · 2016

• NIH Grant R23AM033804

  NIH · $58k · 1987

• NIH Grant R01DK060597

  NIH · $2.8M · 2012

• Diabetes Research Center (DRC)

  NIH · $15.7M · 2002–2028

Frequent coauthors

• Dave Bridges

  University of Michigan–Ann Arbor

  61 shared

• Shannon M. Reilly

  59 shared

• Jeffrey E. Pessin

  40 shared

• Peng Zhao

  The University of Texas Health Science Center at Houston

  31 shared

• Jerrold M. Olefsky

  University of California, San Diego

  30 shared

• Christopher Liddle

  University of Sydney

  29 shared

• Louise Chang

  Michigan United

  28 shared

• Frank W. Sellke

  Brown University

  25 shared

Labs

• Saltiel LabPI

Education

• Ph.D., Molecular and Cell Biology

  University of California, San Diego

  1987

• B.S., Biology

  University of California, San Diego

  1982