[Lecture Note] Metabolic signaling in cell fate decisions

Energy homeostasis and metabolic heath

Food intake (Energy uptake)

Browning of adipose tissue (Energy expenditure)

The cold enviroment lead to energy expenditure

低温导致小鼠肠道菌发生变化，能激活棕色脂肪组织产热机制

We can get : Cold exposure enlarges the gut

Intestinal plasticty 肠道可塑性

Cold microbiota permits increased gut and absorption

寒冷环境塑造的肠道菌群，能够促进肠道发育、提升营养吸收能力

Gut enlarged through reduced apoptosis

肠道体积增大，机制是细胞凋亡水平下降

Specific bacteria prevents gut elongation

Gut microbiota regulates cell apoptosis rate in small intestine.

Genetically obes mice overeat and have longer gut, maybe :

image-20260731141338107

The intestianl surface expands in obese mice

肥胖小鼠的肠道吸收表面积发生扩张

Gut expansion is metabolically costly

肠道扩张具备高昂的代谢代价

Turnover rate : 3-5 days

目前寒冷现象和肠道菌相呼应

Conclusion : Metabolic drivers of gut expansion

Intestinal Pparea KO (I-KO) blunts adaptive small intestinal growth.

肠上皮特异性敲除 Ppara（I-KO）会抑制小肠适应性增生

PPARa I-KO reduces intestinal lipid uptake and droplet generation

Why happening ?

Lead to Reduction of intestinal lipid uptake -> iimproved systemic lipid homeostasis

肠道脂质摄取减少 → 改善全身脂质稳态

A conclusion :

image-20260731142301278

Outstanding questions :

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We lack mechanistic knowledge

Lipid droplets : a switch in adipocyte cell fate 脂肪命运转化开关

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Many facets of lipid droplets - different functions !

  • Organisms
  • Tissues
  • Homologies

Lipid droplets are essential in nervous system

  • Physiological conditions
  • Pathological conditions

There are two classes of LD proteins

  1. ER 2 LD
  2. Cyt. 2 LD

Different perilipins (PLINs) coat lipid droplets

Induction of distinct LD populations in adipocytes

How do PLIJs target different LD populations ?

image-20260731143233064

Endogenous PLIN1 moves between the ER and LD early in adipocyte differentiation

Secondary LDs form only after the switch

Seipin loss in adipocytes and across tissues

脂肪细胞及多组织中 Seipin（BSCL2）缺失引发的生物学效应

image-20260731143808161

Seipin KO prevents PLIN1-LD accumulation

Premature ATGL loading causes constitutive lipolysis in seipin KO

Seipin switch : biochemical and cell biologcal, NOT transcriptional

Seipin - PLIN1 switch : signal to establish adipocyte indentity

Future Work : Cellular control of tissue plasticity

Cell fates and metabolic switches

image-20260731144545186

Traditional : Transcription

New : Metabolic switch (CEll contacts + Metabolites)

Metabolic control points : key for health