(Over)weight and genes
In recent decades the percentage of people who are overweight has grown steadily. Until not so long ago, the general wisdom was that every pound had gone in through the mouth. That turns out to be somewhat more complicated at times. Other factors such as gut flora, genetics, toxins, nutrition, inflammation, hormones and stress also turn out to play a role. It seems that clusters of genes in combination with environmental factors increase the chances of being overweight and make losing weight more difficult.
Stress
With stress, the adrenaline level in the blood rises immediately, followed by the cortisol level. With persistent stress, raised cortisol levels can cause insulin resistance. As a result, the normal mechanism, in which a raised blood glucose causes small amounts of insulin to supply muscle cells and the brain with fuel, does not function properly. Cells have become less sensitive to insulin, so the body responds by driving up insulin levels, with the result that too much glucose is taken up into fat cells. As long as insulin is high, fat cells will not release fats into the bloodstream and fat burning cannot get started.
Stress, especially prolonged stress, also affects digestion. The blood supply to the intestines is greatly reduced, and with it the intestinal peristalsis and the release of digestive enzymes. The composition of the gut flora changes and the permeability of the intestinal wall can increase. As a result, cell wall fragments of bacteria (LPS and LTA) can activate immune cells and cause Low Grade Inflammation. Low Grade Inflammation can cause overweight. Fatty tissue itself is also a source of inflammatory factors and maintains the status of Low Grade Inflammation (1-7).
A large number of genes are involved in inflammatory cascades, and thanks to genetic variations the effectiveness of this system can lead to considerable differences. An immune system that reacts too strongly can make losing weight more difficult. With knowledge of the genetic predisposition, targeted therapy can be used.
Detoxification
Many toxins are difficult or impossible to break down and are highly fat-soluble. They are stored en masse in fatty tissue (8). Toxic substances cause oxidative stress and inflammation. Inflammation makes you insulin resistant and hinders weight loss (9). Many toxins are called obesogens or hormone disruptors. They disrupt, among other things, thyroid function and mitochondrial combustion, and thus the ability to burn fat (10).
When you lose weight, the stored toxins are released again and will still have to be removed. That puts great pressure on the detoxification and antioxidant system. If these processes do not run well, strongly oxidising intermediate products will cause oxidative stress, which makes losing weight more difficult (11, 12).
People’s ability to detoxify and to counteract oxidation can differ greatly, partly as a result of genetic predisposition. Targeted support based on the genetic profile can improve these processes.
Oestrogens
Methylation is an essential process in which the MTHFR enzyme plays a crucial role. Partly via MTHFR, homocysteine is converted into methionine, which in turn can be used to make SAM, the universal methyl donor. Without a well-functioning methylation, and effective enzymes such as COMT, neurotransmitters and hormones such as oestrogens are insufficiently broken down. In the production of oestrogens, too, there are genetic differences between people.
When the balance between oestrogens and progesterone is disturbed we speak of oestrogen dominance; there is an excess of strongly acting oestrogens. Oestrogen dominance can cause stubborn accumulations of fat on the buttocks, thighs, abdomen and breasts (13-17).
By mapping the genetic sensitivity to oestrogen dominance, insight is gained into the balance between the production and the breakdown/removal of oestrogens. Targeted support thus becomes possible and can be helpful in losing weight.
In summary
In overweight, the influence of eating and exercise patterns, hormonal factors and the gut flora are important factors. In addition, there are people who, despite an exemplary lifestyle, still do not lose weight, or hardly. This can be caused in part by the genetic constitution. Insight into the genetic profile can provide handholds for meaningful and targeted support.
Literature
1 The Gut Microbiome: What we do and don’t know, Gail A. Cresci,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838018/
2 Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation
https://pubmed.ncbi.nlm.nih.gov/33539766/
3 Gut barrier disruption and chronic disease , Jan Martel,
https://pubmed.ncbi.nlm.nih.gov/35151560/
4 Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes , Torsten P M Scheithauer,
https://pubmed.ncbi.nlm.nih.gov/33178196/
5 Inflammatory mechanisms linking obesity and metabolic disease , Alan R Saltiel, Jerrold M Olefsky
https://pubmed.ncbi.nlm.nih.gov/28045402/
6 The Gut Microbiome: What we do and don’t know, Gail A. Cresci, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838018/
7 Gut barrier disruption and chronic disease , Jan Martel,
https://pubmed.ncbi.nlm.nih.gov/35151560/
Inflammatory response to dietary linoleic acid depends on FADS1 genotype , Maria A Lankinen, 2019.
8 The influence of persistent organic pollutants in the traditional Inuit diet on markers of inflammation, L. K. Schæbel, 2017
9 Toxic environment and obesity pandemia: Is there a relationship? Giuseppe Latini, 2010
10 The Perfect Storm for Obesity, Jerrold J. Heindel, 2017
11 GSH levels affect weight loss in individuals with metabolic syndrome and obesity following dietary therapy, Nikolaos Goutzourelas, 2018
12 Adipose Tissue as a Site of Toxin Accumulation, Erin Jackson, 2017, The Perfect Storm for Obesity, Jerrold J. Heindel, 2017
13 Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women , Irene Lambrinoudaki, 2008
14 Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women C Worda, 2003,
https://pubmed.ncbi.nlm.nih.gov/12571159/
15 Influence of Estrogenic Metabolic Pathway Genes Polymorphisms on Postmenopausal Breast Cancer Risk, Micaela Almeida, 2021
16 The role of oestrogen in the pathogenesis of obesity, type 2 diabetes, breast cancer and prostate disease, Graeme P. Williams https://www.jstor.org/stable/48503973