Stops fat storage
De-novo lipogenesis↓
Also searched as De-novo lipogenesis.
You want it quiet: restraining lipogenesis is how the liver and waistline stay lean.
In depth
Fatty-acid synthesis — the de-novo line that converts surplus carbohydrate into stored fat and liver triglyceride.
What drives it
Energy sensing reduces it.
Li 2011, Cell Metab 13:376 — AMPK phosphorylates ACC and SREBP-1c, suppressing hepatic de novo lipogenesis. Mouse + HepG2 in vitro. Asymmetric: a later paper reports AMPK re-activation suppresses hepatic steatosis but its downregulation does not promote fatty liver, and finds NO correlation between lipogenic gene expression and intracellular triglyceride (PMC5835560). Raising AMPK helps; lowering it does not cause the disease. Two separate mechanisms, acute and transcriptional. Acute: AMPK phosphorylates and inhibits ACC1, the rate-limiting enzyme of fatty-acid synthesis (Davies 1992; Munday 1988). Transcriptional: AMPK also down-regulates expression of lipogenic enzymes by phosphorylating and inhibiting SREBP-1c (Li 2011). It additionally inhibits HMG-CoA reductase, so the same switch restrains cholesterol synthesis. the SREBP-1c arm is stated with 'possibly' in the source — the acute ACC1 arm is the secure one. PMC5835560
Fasting insulin increases it.
Insulin is the signal that tells the liver to make fat: hepatic insulin resistance together with dietary monosaccharides raises delivery to the liver and stimulates SREBP-1c, which drives hepatic DE novo lipogenesis (PMC7663738). This is the step that then lowers HNF-4α and SHBG downstream — the same chain, one link earlier. PMC7663738
Central fuel molecule increases it.
The substrate for fatty acid synthesis. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
The Factory Order reduces it.
PMID 21356515 — Same sentence: IRF4 promotes fat melting and suppresses lipid biosynthesis. One switch, two directions. The source frames adipose triacylglycerol content as the balance between biosynthesis and melting, with IRF4 setting that balance (ライフサイエンス 新着論文レビュー (first.lifesciencedb.jp/archives/2444)). PMID 21356515
Where glycerol goes increases it.
10.1002/advs.202401311 — The futile cycle has a second, whole-body arm — and it was the german reference that named it. 'Das in der Lipolyze entstandene Glycerin wird ebenfalls von der Leber abgebaut und zur GLUCONEOGENESE oder FETTSÄURESYNTHESE herangezogen' = the glycerol produced by lipolysis is broken down by the liver and used for gluconeogenesis OR fatty-acid synthesis (flexikon.doccheck.com/de/Lipolyze (deutsch)). ⇒ the re-esterification node covers what is recaptured inside the fat cell. This is what is recaptured after it has left: the glycerol travels to the liver and can be rebuilt into fatty acids there. The consequence for every glycerol measurement in this formula: glycerol appearing in blood proves fat left the cell. It does not prove fat left the body. Almost every driver here is graded on glycerol release, and that is the honest ceiling on what those numbers mean. The source names two destinations, and only one is drawn here: the liver routes released glycerol into new glucose as well as into new fat. The glucose arm is the benign one. Which arm dominates depends on the fed or fasted state — one more reason this product's own evidence says fasted. The glucose arm is not shown as a separate connection here. doi 10.1002/advs.202401311
Acetaldehyde load increases it.
Verbatim (pmc12086950): 'Key transcription factors that regulate de novo lipogenesis are sterol regulatory element binding protein 1c (SREBP-1c), early growth response-1 (Egr-1) and carbohydrate response element binding protein (ChREBP) are all activated by chronic alcohol in the liver. Activation of SREBP-1c induces lipogenic genes such as fatty acid synthase (FAS), acyl coA carboxylase (ACC-1 and ACC-2), ATP citrate LYASE (ACL) and STEAROYL COA DESATURASE (SCD-1).'.
What it drives
It increases Ceramide first step.
Ceramide-metabolism review 2016, Am J Physiol Endocrinol Metab - palmitate, the product of de novo lipogenesis via fatty-acid synthase, is the substrate serine palmitoyltransferase condenses with serine. Lipid oversupply therefore feeds ceramide synthesis at its first committed step, which is the mechanical link between eating pattern and this pathway. Sources:. PMID 28280233
It increases Ceramide load.
Ceramide-metabolism review 2016, Am J Physiol Endocrinol Metab — palmitate, the product of de novo lipogenesis (fatty-acid synthase), is the substrate for de novo ceramide synthesis, so lipid oversupply drives ceramide accumulation. doi 10.1152/ajpendo.00133.2016
It increases Clears liver fat.
Li 2011, Cell Metab 13:376 — SREBP-1c-driven de novo lipogenesis accumulates hepatic triglyceride; blocking it attenuates steatosis. Mouse. lipogenic gene expression did not correlate with intracellular triglyceride accumulation across AMPK activators (PMC5835560) -- the transcriptional step and the lipid outcome can dissociate. PMC5835560
It increases Triglycerides.
SREBP-1c lipogenic program — ACC and FAS synthesize fatty acids that are esterified into triglycerides. Li 2011, Cell Metab 13:376. Mouse + HepG2. Same dissociation caveat as above. PMC5835560
It reduces Hormone-binding protein.
This — not insulin by itself — is the proximate mechanism. Monosaccharides (glucose and fructose) reduce human SHBG production by hepatocytes by downregulating HNF-4α, the transcription factor that drives the SHBG promoter; and the causal step is lipogenesis, because inhibiting lipogenesis prevented the monosaccharide-induced fall in HNF-4α and in SHBG (Selva et al., PMID 17992261). Hepatic insulin resistance and dietary sugar raise monosaccharide delivery to the liver, stimulate SREBP-1c and de-novo lipogenesis, and lower HNF-4α and SHBG with it. PMID 17992261 · PMC7663738
It reduces Insulin sensitivity.
insulin, fasting insulin, type 2 diabetes and blood lipids share one literature: heart, kidney, liver, and metabolic diseases share interlinked pathological mechanisms, including inflammation, oxidative stress, insulin resistance, and endothelial health issues. These four overlap by nature: fasting insulin is the level, insulin is the signaling, type 2 diabetes is the diagnosis and blood lipids are the substrate. The same driver legitimately reaches all four, and a reader should not mistake four arrows for four independent findings. doi 10.1038/s41581-026-01066-0 · PMC11725408
It reduces Lowers cholesterol.
insulin, fasting insulin, type 2 diabetes and blood lipids share one literature: heart, kidney, liver, and metabolic diseases share interlinked pathological mechanisms, including inflammation, oxidative stress, insulin resistance, and endothelial health issues. These four overlap by nature: fasting insulin is the level, insulin is the signaling, type 2 diabetes is the diagnosis and blood lipids are the substrate. The same driver legitimately reaches all four, and a reader should not mistake four arrows for four independent findings. doi 10.1038/s41581-026-01066-0 · PMC11725408
It reduces Liver.
10.1172/JCI23621 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD”. doi 10.1172/JCI23621 · PMID 31805015 · PMC7269561
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.