CICO is properly applied to a system defined by a boundary. The complete equation is:
inputs—outputs = accumulation + depletion (adjust signs as needed)
where these parameters are as compared to the system boundary.
Inputs for a mammal system are food, water, oxygen, and heat. Outputs are heat, sweat, urine, feces and CO2. Accumulation/depletion within the system would include muscle, fat, plasma, bone, organs, and microbial ecosystem.
Energy inputs to the system can go to the primary host body (e.g. fat accumulation) or to the microbes’ ecosystem or output in sweat, urine/feces or heat. The microbial ecosystem requires energy and dietary components as it blooms, changes, dies-off, etc.
Most of the posts/commentary I’ve seen in the rationalist arenas have never mentioned “CICO” system analyses that include intestinal microbial ecosystem or urinary/fecal output. Here are some studies that address those two areas of the system analysis:
doi:10.1093/ajcn/31.7.1149 “Metabolic Effects of Fiber” Human cross-over design comparing fiber intake. Two diets with the same total kcal, protein, fat. Carb difference of about 20gms and in the amount of fiber: lower vs higher. Almost 1000 kcal more calories excreted in feces with the higher fiber diet compared to lower. About 10gms more fat excreted in feces with higher vs lower fiber diet.
DOI: 10.1016/j.tem.2020.06.002 “Role of Energy Excretion in Human Body Weight Regulation”
DOI:10.1097/MCO.0000000000000696 “Dietary fibers reduce obesity-related disorders: mechanisms of action.” “Dietary fiber prevents and treats obesity-related disorders. Mechanisms for this protection include decreased absorption of macronutrients and enhanced satiety. Changes in the gut microbiota and short-chain fatty acids are emerging mechanisms to explain why high fiber diets protect against obesity and have a role in obesity treatment.”
DOI: 10.1080/10643389.2014.1000761 “The Characterization of Feces and Urine: A Review of the Literature to Inform Advanced Treatment Technology” Includes tables of data from, for example, high/low income countries vs fecal mass output, references to diet type vs fecal mass output, factors affecting fecal output.
Example scholar.google search terms “fiber mechanisms obesity”
From the microbial ecosystem factors side of the “CICO” systems analysis:
doi: 10.1073/pnas.0407076101 “The gut microbiota as an environmental factor that regulates fat storage”
doi: 10.1038/nature11552 “Functional interactions between the gut microbiota and host metabolism”
doi: 10.1073/pnas.0808567105 “Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, GPR41”
doi: 10.1038/nature18846 “Diet-microbiota interactions as moderators of human metabolism”
doi: 10.1038/s41591-020-0801-z “Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans” …”These results indicate that nutrient absorption is sensitive to environmental perturbations and support the translational relevance of preclinical models demonstrating a possible causal role for the gut microbiome in dietary energy harvest.”
DOI: 10.1126/science.1241214 “Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice” …”These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.”
doi: 10.3945/ajcn.110.010132 “Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans” This is an human, inpatient clinical trial. …”Furthermore, the observed associations between gut microbes and nutrient absorption indicate a possible role of the human gut microbiota in the regulation of the nutrient harvest.”
DOI: 10.1113/jphysiol.2009.174136 “The core gut microbiome, energy balance and obesity” Comparison of human mono- and dizygotic obese and lean adult human twins.
doi: 10.1073/pnas.0605374104 “Mechanisms underlying the resistance to diet-induced obesity in germ-free mice” Mice without microbes don’t become obese when fed a Western-style, high-fat, sugar-rich diet. Conventional mice do become obese on the same diet.
scholar.google search terms: “microbes mechanisms obesity”
There is a lot more in this area of the system analysis. I’m going to stop here for now.
Thank you for taking the time to explore this domain.
There is at least one additional aspect of lipid structure consumption that is not part of your list of mechanisms. Lipid shape affects the shape of membranes. This paper illustrates the concept (tldr: Figures 3 & 4):
https://dasher.wustl.edu/bio5357/readings/naturerevmcb-19-281-18.pdf “Understanding the diversity
of membrane lipid composition”
Figure 3 in the following review paper shows a table of different physical properties for the endoplasmic reticulum (ER), Golgi apparatus, and plasma membrane (PM) and their % of different lipid shapes that drive their function:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892264/ “Regulation of membrane protein structure and function by their paralipidomes”
Not commenting on the 5 mechanisms explained above. Just noting another possible mechanism for an effect of ingesting different proportions of lipid structures. Ingested lipid shape shapes membrane shapes and, subsequently, lipid-lipid and lipid-protein interactions.
Agree with the complexity aspect of biology.