How To Fatten A Mammal

This video serves as a sort of road map of Fire In A Bottle topics. On the blog and video series I’ve drilled into numerous topics and their relationship with obesity: PUFA, MUFA, The ROS Theory of Obesity, reductive stress, D6D, SCD1, the AhR, PPAR alpha, etc.

Sometimes it’s useful to zoom out and see the forest. This video serves as a roadmap with squirrels and oak trees serving as the central characters. The oaks need to squirrels to spread their seeds. Also known as acorns. The squirrels need to fatten up for winter.

Black and red oak acorns have evolved to be perfectly fattening. The percent of calories break down as:

Acorn (% of Cals)High-Fat DietCroissant
Carbohydrate483547
Protein6.6208
Fat464545
MUFA272012
PUFA1281

In red oak acorns, fat provides 46% of calories with 27% of calories as MUFA and 12% as PUFA, leaving only 7% of calories as saturated fat. This is remarkably similar (although lower in protein) to the “High-Fat Diet” that is consistently used to create obesity and insulin resistance in lab rats. On the other hand, acorns are much higher in MUFA and PUFA than the butter croissants that have kept the French lean.

This video explains why the acorns have chosen this particular composition to fatten squirrels from a molecular perspective. References are below.

References

Adina-Zada A, Zeczycki TN, Attwood PV (2012) Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA. Archives of Biochemistry and Biophysics 519:118–130. https://doi.org/10.1016/j.abb.2011.11.015

Bemmels JB, Dick CW (2018) Genomic evidence of a widespread southern distribution during the Last Glacial Maximum for two eastern North American hickory species. J Biogeogr 45:1739–1750. https://doi.org/10.1111/jbi.13358

Diamond SJ, Giles RH, Kirkpatrick RL, Griffin GJ (2000) Hard Mast Production Before and After the Chestnut Blight. Southern Journal of Applied Forestry 24:196–201. https://doi.org/10.1093/sjaf/24.4.196

Fisher-Wellman KH, Lin C-T, Ryan TE, et al (2015) Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy-consuming redox circuit. Biochemical Journal 467:271–280. https://doi.org/10.1042/BJ20141447

Fu X, Fletcher JA, Deja S, et al (2023) Persistent fasting lipogenesis links impaired ketogenesis with citrate synthesis in humans with nonalcoholic fatty liver. Journal of Clinical Investigation 133:e167442. https://doi.org/10.1172/JCI167442

Guerre-Millo M, Rouault C, Poulain P, et al (2001a) PPAR-α–Null Mice Are Protected From High-Fat Diet–Induced Insulin Resistance. Diabetes 50:2809–2814. https://doi.org/10.2337/diabetes.50.12.2809

Guerre-Millo M, Rouault C, Poulain P, et al (2001) PPAR-α–Null Mice Are Protected From High-Fat Diet–Induced Insulin Resistance. Diabetes 50:2809–2814. https://doi.org/10.2337/diabetes.50.12.2809

Gurnell J (1983) Squirrel numbers and the abundance of tree seeds. Mammal Review 13:133–148. https://doi.org/10.1111/j.1365-2907.1983.tb00274.x

Liu J, Cinar R, Xiong K, et al (2013) Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase. Proc Natl Acad Sci USA 110:18832–18837. https://doi.org/10.1073/pnas.1309469110

Lounis MA, Bergeron K-F, Burhans MS, et al (2017) Oleate activates SREBP-1 signaling activity in SCD1 -deficient hepatocytes. American Journal of Physiology-Endocrinology and Metabolism 313:E710–E720. https://doi.org/10.1152/ajpendo.00151.2017

Maccarrone M, Pauselli R, Di Rienzo M, Finazzi-AgrĂČ A (2002) Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells. Biochemical Journal 366:137–144. https://doi.org/10.1042/bj20020438

McCarthy MA, Meredith FI (1988) Nutrient data on chestnuts consumed in the United States. Econ Bot 42:29–36. https://doi.org/10.1007/BF02859026

Moller H (1983) Foods and foraging behaviour of Red (Sciurus vulgaris) and Grey (Sciurus carolinensis) squirrels. Mammal Review 13:81–98. https://doi.org/10.1111/j.1365-2907.1983.tb00270.x

Ntambi JM, Miyazaki M, Stoehr JP, et al (2002) Loss of stearoyl–CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99:11482–11486. https://doi.org/10.1073/pnas.132384699

Oscarsson J, Önnerhag K, RisĂ©rus U, et al (2018) Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A double-blind, randomized, placebo-controlled study. Journal of Clinical Lipidology 12:1390-1403.e4. https://doi.org/10.1016/j.jacl.2018.08.003

Panuska JA (1959) Weight Patterns and Hibernation in Tamias striatus. Journal of Mammalogy 40:554. https://doi.org/10.2307/1376275

Pettit FH, Pelley JW, Reed LJ (1975) Regulation of pyruvate dehydrogenase kinase and phosphatase by acetyl-CoA/CoA and NADH/NAD ratios. Biochemical and Biophysical Research Communications 65:575–582. https://doi.org/10.1016/S0006-291X(75)80185-9

Pickens CA, Sordillo LM, Comstock SS, et al (2015) Plasma phospholipids, non-esterified plasma polyunsaturated fatty acids and oxylipids are associated with BMI. Prostaglandins, Leukotrienes and Essential Fatty Acids 95:31–40. https://doi.org/10.1016/j.plefa.2014.12.001

Pi-Sunyer FX, Aronne LJ, Heshmati HM, et al (2006) Effect of Rimonabant, a Cannabinoid-1 Receptor Blocker, on Weight and Cardiometabolic Risk Factors in Overweight or Obese Patients: RIO-North America: A Randomized Controlled Trial. JAMA 295:761. https://doi.org/10.1001/jama.295.7.761

Powell D, Gay J, Smith M, et al (2016) Fatty acid desaturase 1 knockout mice are lean with improved glycemic control and decreased development of atheromatous plaque. DMSO 185. https://doi.org/10.2147/DMSO.S106653

Rojas IY, Moyer BJ, Ringelberg CS, Tomlinson CR (2020) Reversal of obesity and liver steatosis in mice via inhibition of aryl hydrocarbon receptor and altered gene expression of CYP1B1, PPARα, SCD1, and osteopontin. Int J Obes 44:948–963. https://doi.org/10.1038/s41366-019-0512-z

Senter SD, Payne JA, Miller G, Anagnostakis SL (1994) Comparison of total lipids, fatty acids, sugars and nonvolatile organic acids in nuts from fourCastanea species. J Sci Food Agric 65:223–227. https://doi.org/10.1002/jsfa.2740650216

Shoieb SM, El-Kadi AOS (2020) Resveratrol attenuates angiotensin II-induced cellular hypertrophy through the inhibition of CYP1B1 and the cardiotoxic mid-chain HETE metabolites. Mol Cell Biochem 471:165–176. https://doi.org/10.1007/s11010-020-03777-9

Short HL (1976) Composition and Squirrel Use of Acorns of Black and White Oak Groups. The Journal of Wildlife Management 40:479. https://doi.org/10.2307/3799950

Short HL, Duke WB (1971) Seasonal Food Consumption and Body Weights of Captive Tree Squirrels. The Journal of Wildlife Management 35:435. https://doi.org/10.2307/3799694

Silva JF, Bolsoni JA, Costa RM, et al (2022) Aryl hydrocarbon receptor (AhR) activation contributes to high‐fat diet‐induced vascular dysfunction. British J Pharmacology 179:2938–2952. https://doi.org/10.1111/bph.15789

Sugden MC, Holness MJ (2006) Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases. Archives of Physiology and Biochemistry 112:139–149. https://doi.org/10.1080/13813450600935263

Wauters LA, Dhondt AA (1989) Variation in length and body weight of the red squirrel( Sciurus vulgaris ) in two different habitats. Journal of Zoology 217:93–106. https://doi.org/10.1111/j.1469-7998.1989.tb02477.x

Xiong Y, Liu Z, Zhao X, et al (2018) CPT1A regulates breast cancer-associated lymphangiogenesis via VEGF signaling. Biomedicine & Pharmacotherapy 106:1–7. https://doi.org/10.1016/j.biopha.2018.05.112