Tag: Understanding Obesity

Is Obesity a Brain Problem? How the Body Controls Weight

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Patients ask me some version of this constantly: “Why can’t I just eat less and lose the weight?” On the surface it sounds like a fair question. Obesity is a chronic disease with a great deal of biology behind it, and the brain sits at the center of that biology. Treatment that ignores this tends to fail, and the patient usually gets blamed for the failure.

Research from Dr. Sabrina Diano at Columbia University lays out how the brain regulates weight and why it matters clinically.

The central nervous system runs energy balance through two systems. The hypothalamus handles hunger and fullness, the homeostatic side. The hedonic pathway, running on dopamine, responds to reward. That second system is why cravings and emotional eating feel as forceful as they do (Lenoir et al., 2007; Samaha et al., 2020).

Within the hypothalamus, the arcuate nucleus holds two opposing groups of neurons. NPY/AgRP neurons drive eating when energy runs low. POMC/α-MSH neurons suppress appetite when energy is adequate. Both communicate with the PVN, VMH, and LH, and the result is a negotiated balance between intake and expenditure (Diano, 2024; Gropp et al., 2005).

The body feeds signals into that system constantly. Fat tissue releases leptin, which should reduce appetite, except that many patients with obesity develop leptin resistance and the signal lands blunted (Zhang et al., 1994). Adiponectin helps regulate insulin and fat metabolism, and levels fall in obesity (Mahmoud, 2022). After meals, insulin, GLP-1, PYY, and amylin generate satiety. Ghrelin, made in the stomach, climbs before meals and drives hunger. In Prader-Willi syndrome it runs abnormally high (Drucker & Holst, 2023).

Diet interferes with the signaling directly. High-fat, high-sugar foods provoke inflammation in the hypothalamus that disrupts how these neurons talk to each other, through oxidative stress and breakdown of melanocortin pathways (Kim et al., 2019; Diano, 2023). Obesity also generates low-grade inflammation throughout the body, visceral fat especially, which worsens insulin resistance (Mukherjee et al., 2023).

Genetics complicates it further. A few single-gene mutations cause obesity outright, but most cases involve many genes each nudging risk slightly. Epigenetics matters too: maternal obesity during pregnancy can alter gene expression in the child and raise their risk decades later (Farooqi et al., 2003; Mahmoud, 2022; Catalano & Shankar, 2017).

The gut microbiome is another piece, with lower microbial diversity and more gut inflammation both tracking with obesity (Vezza et al., 2020). Environmental chemicals including BPA and phthalates can disrupt hormone signaling and tilt the body toward storing fat (Heindel et al., 2015).

All of this explains the part patients find most demoralizing, which is why weight loss is so hard to hold onto. The body defends a set point. Weight comes down, metabolism slows, hunger hormones rise, and regain becomes the likely outcome (Diano, 2024).

Consider what that looks like in practice. Someone loses 20 pounds through real effort, and then finds themselves hungrier than they have ever been while burning fewer calories at rest. Nothing about their discipline changed. Their body is defending the weight it had before.

Recognizing obesity as a biologically regulated condition changes the approach. Treatment has to work on several fronts at once: nutrition, behavioral strategy, medication, and sometimes surgery. GLP-1 receptor agonists like liraglutide and semaglutide, and dual agonists like tirzepatide, act on these pathways directly, which is a large part of why they work as well as they do.

Obesity is physiology, environment, and genetics interacting. Personal choice is in there somewhere, well downstream of the rest. Understanding that gives us better tools and considerably more patience.

Scott Rennie, D.O.

References

Diano, S. Physiology and Pathophysiology of Obesity, Columbia University, 2024.

Zhang Y, et al. Nature, 1994;372(6505):425-32.

Gropp E, et al. Nature Neuroscience, 2005;8(10):1289-91.

Farooqi IS, et al. NEJM, 2003;349(6):570-8.

Drucker DJ, Holst JJ. Diabetologia, 2023;66(4):651-64.

Kim DW, et al. Cell Metabolism, 2019;30(1):110-122.

Mukherjee R, et al. Front Endocrinol, 2023;14:1154067.

Heindel JJ, et al. Nat Rev Endocrinol, 2015;11(11):653-61.

Mahmoud AM. Int J Mol Sci, 2022;23(3):1225.

Catalano PM, Shankar K. BMJ, 2017;356:j1.

Vezza T, et al. Antioxidants, 2020;9(7):578.

Lenoir M, et al. PLoS One, 2007;2(8):e698.

Samaha AN, et al. Neurosci Biobehav Rev, 2020;113:198-213.

Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

How Processed Food Disrupts the Gut Brain Connection

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

For years we told patients obesity came down to calories in and calories out. The research has moved. The gut-brain axis, the two-way traffic between the digestive system and the central nervous system, sits at the center of hunger, satiety, and reward. When it works, it regulates intake without conscious effort. Against the current food supply, it often doesn’t work.

The axis runs on neural, hormonal, and metabolic signals. After a meal, the gut reports what came in, how much, and when to stop. That system evolved for whole foods and scarce calories. It was never built for a diet dominated by processed, energy-dense products.

Alexandra DiFeliceantonio and Dana Small have argued that modern food disrupts the system by creating mismatches between what the gut senses and how the brain responds (Small & DiFeliceantonio, Science, 2019). Three features stand out.

The first is macronutrient combination. Fat and refined carbohydrate rarely appear together in high amounts in nature. Most processed food delivers both. People assign higher value to fat-carb combinations even when calories are held constant. In one controlled experiment, participants bid more money for foods containing both than for foods containing either alone (DiFeliceantonio et al., Cell Metab, 2018).

Speed of absorption is the second. Highly processed foods deliver calories fast, producing stronger responses in glucose metabolism and reward pathways (Carmody et al., PNAS, 2011; Hall et al., Cell Metab, 2019). Rodents develop stronger preferences for rapidly metabolized foods. In humans, faster eating rate tracks with weight gain.

Additives are the third. Sweeteners, emulsifiers, and artificial flavors make food more palatable while confusing the signaling underneath. When sweet taste stops reliably predicting calorie content, the brain loses the ability to regulate intake based on prior experience (Dalenberg et al., Cell Metab, 2020). The body learns that taste no longer matches nutrition.

The evidence supports the picture. People with obesity show altered valuation of high-reward foods compared with lean individuals (Perszyk et al., Nutrients, 2021). Rodents fed cafeteria-style diets full of energy-dense processed food overeat and gain weight, while chow-fed controls hold steady (Johnson & Kenny, Nat Neurosci, 2008; Beilharz et al., Front Psychol, 2014). Neuroimaging shows the striatum responding differently to fat-carb combinations than to single macronutrients (DiFeliceantonio et al., 2018).

All of which points at something uncomfortable. The modern food environment may overwhelm and distort the very systems built to keep intake in check. That is a real explanation for why “eat less, move more” fails so often. The advice assumes intact gut-brain signaling in people whose signaling is already compromised.

The open research question is how to restore it. Diets built around foods that reinforce reliable gut-brain communication. Studies of how additives affect hormonal and neural markers of satiety. Behavioral work helping patients relearn hunger and fullness cues.

Clinically, the thing worth holding onto is the environment patients are choosing inside. A food supply engineered to exploit biological vulnerabilities will beat most people’s intentions, and restoring the fidelity of that signaling may be where the real leverage sits.

Scott Rennie, D.O.

References:

1. Small DM, DiFeliceantonio AG. Processed foods and food reward. Science. 2019;363(6425):346-347. https://pubmed.ncbi.nlm.nih.gov/30679360/

2. DiFeliceantonio AG, et al. Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward. Cell Metab. 2018;28(1):33-44.e3. https://pubmed.ncbi.nlm.nih.gov/29909968/

3. Carmody RN, Weintraub GS, Wrangham RW. Energetic consequences of thermal and nonthermal food processing. Proc Natl Acad Sci USA. 2011;108(48):19199-19203. https://pubmed.ncbi.nlm.nih.gov/22065771/

4. Hall KD, et al. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain. Cell Metab. 2019;30(1):67-77.e3. https://pubmed.ncbi.nlm.nih.gov/31105044/

5. Dalenberg JR, et al. Short-Term Consumption of Sucralose with, but not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans. Cell Metab. 2020;31(3):493-502.e7. https://pubmed.ncbi.nlm.nih.gov/32130879/

6. Perszyk EE, et al. Nutrients. 2021;13(11):3846.

7. Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13(5):635-641. https://pubmed.ncbi.nlm.nih.gov/20348917/

8. Beilharz JE, Maniam J, Morris MJ. Front Psychol. 2014;5:1454.

Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.