Tag: Set Point Theory

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.

Is Yo-Yo Dieting Bad for You? Weight Cycling Explained

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

A lot of my patients describe the same arc. They work hard, lose weight, feel good for a while, and then months or years later it comes back. That repeated loss and regain is weight cycling. It is common, and it is hard on people both physically and emotionally.

The question I hear most often is whether it is even worth trying if the weight is coming back anyway. The research answers that more clearly than it used to, and the answer is yes.

Weight cycling generally means repeated intentional loss followed by unintentional regain. Some researchers set the bar at a 10 percent change in body weight occurring three or more times. Depending on the study, it affects 20 to 35 percent of men and up to half of women (Montani et al., 2015).

Why does the weight return? Biology pushes back harder than most people anticipate. After weight loss, resting energy expenditure falls further than body size alone would predict, and this metabolic adaptation can persist for years, meaning the body burns less than expected (Fothergill et al., 2016). Hormones move too. Leptin drops, hunger hormones climb, and patients end up hungrier and less satisfied by meals than they were before (Sumithran et al., 2011). The body also tends to compensate for exercise by raising appetite. Together these explain why maintenance is the hard part, not the losing (Thomas et al., 2012).

The real question is whether the cycling itself does damage. Large reviews and cohort studies have not found strong evidence that weight cycling raises mortality or major chronic disease risk when the weight loss is intentional and supervised (Mehta et al., 2014). Some work suggests regain may favor fat over muscle, visceral fat especially, though the findings are inconsistent (Mackie et al., 2017).

The psychological picture is better than most people assume. Foster and colleagues found that patients who regained weight still reported improvements in mood, hunger, and eating behavior after the loss phase (Foster et al., 1996). Other work has found no consistent long-term harm from the pattern itself (Osborn et al., 2011).

So should patients keep trying? The National Task Force on the Prevention and Treatment of Obesity concluded in 1994 that weight cycling should not deter people from attempting weight loss, and that position has held up (National Task Force, JAMA 1994). The benefits of intentional loss, lower blood pressure, better lipids, better glucose control, better quality of life, generally outweigh the risk of regaining.

One of my patients lost about 8 percent of her body weight through diet and walking. A year later most of it had come back. During the stretch she kept it off, though, her blood pressure normalized and she came off one of her antihypertensives. The weight returned. The benefit she got during that window was real and measurable, and the research says her experience is the rule rather than the exception.

What I steer patients toward is sustainable habit rather than another aggressive diet. Regular activity, consistent eating patterns, decent sleep, and watching the trend line instead of the daily number. A setback does not undo the progress. Staying connected to support, whether that is a clinician, a dietitian, or counseling, matters more than most people expect.

Weight cycling is real and it is discouraging. It is not a reason to stop. Even temporary weight loss buys real health, and the useful reframe is to treat weight management as ongoing care rather than a project with an end date.

Scott Rennie, D.O.

References

Montani JP et al. Obesity Reviews. 2015.

Fothergill E et al. Obesity. 2016.

Sumithran P et al. NEJM. 2011.

Thomas DM et al. Obesity. 2012.

Mehta T et al. Obesity Reviews. 2014.

Mackie GM et al. Obes Res Clin Pract. 2017.

Foster GD et al. J Consult Clin Psychol. 1996.

Osborn CY et al. Ethn Dis. 2011.

National Task Force on the Prevention and Treatment of Obesity. Weight cycling. JAMA. 1994;272(15):1196-1202.

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.