Study finds vitamin B12 deficiency in pregnancy may induce obesity

A new study which was presented at the annual conference of Society for Endocrinology reports that vitamin B12 deficiency could disrupt the normal metabolism of fat and could indirectly contribute to weight gain and obesity in pregnancy. This emphasizes the need supplement this vitamin during pregnancy, because obesity in pregnancy is linked to a number of adverse health outcomes over the long term, including diabetes.

Vitamin B12

Also called cobalamin, vitamin B12 is a substance found in seafood, dairy and meat products. It is an essential cofactor for a number of enzymes, or biological catalysts, that keep the thousands of chemical reactions in the human body running smoothly. When the diet consists mostly of starchy highly-processed foods, vitamin B12 intake is likely to be deficient. Both animal and human studies have indicated that B12 deficiency is linked to an increased risk of the metabolic syndrome.

Studies have shown that this vitamin deficiency affects about a quarter of pregnant women worldwide, because of the increased requirement for fetal development and growth. There has also been some evidence suggesting that this condition increases the risk that the woman will develop obesity or diabetes. However, scientists could not find out how this happens.

Fat cells are fundamental to many chemical reactions in the body, motivating the current attempt to find out how the deficiency of vitamin B12 is related to the impairment of the synthesis of triglycerides, and the altered metabolism of fats in the body. Abnormal fat metabolism is known to cause inflammation within fatty tissue.

The study

The current study looked at the function of fat cells was affected in two settings. In the first, the ABdSc preadipocyte line of cultured cells was grown in culture media with varying levels of vitamin B12, namely, 25 pM, 100 pM, 1 nM, and 500 nM. Another set of cells, called human AbdSc primary preadipocytes, was also grown under the same settings.

As a direct comparison, fat cells derived from the omental (within the belly) and subcutaneous (under the skin) fatty tissues, and blood samples, were also taken from pregnant women with B12 deficiency. After measuring serum B12 and other metabolic risk factors such as blood glucose and lipid concentrations, the researchers studied the Om and Sc-AT cells to discover their metabolic profile.

The scientists looked at the levels of expression of genes that were related to fat metabolism, using quantitative RT-PCR methods. They measured the total amount of triglyceride synthesized, using radioactive tracers to label the substrate chemicals that would be needed for this reaction within the fat cells.

They also determined the level of fatty acid oxidation called beta-oxidation, which reflects the use of fatty acids as a source of energy in the body. Additionally, they examined the oxygen consumption rate within the mitochondria in response to palmitate, a fatty acid. The latter two processes were assessed using the seahorse-XF analyzer which uses live cells to measure metabolic reaction rates.

The findings

The researchers saw that the level of certain chemicals that come from reactions involving fat cells was significantly altered. In other words, the lack of vitamin B12 affected fat cell metabolism. For instance, triglyceride biosynthesis genes such as ELOVL6, and SCD were upregulated, or their activity showed an increase. On the other hand, beta-oxidation genes like FAT/CD36 and CTP1-β showed a drop.

Also, there was a rise in certain chemicals released by the cells as part of their signaling, that is, cytokines. These include interleukins like IL-1, IL-6,IL-8,and IL-18, growth factors like TGF-β, the tumor necrosis factor TNF-α and immune cell recruitment factors like MCP-1. These are known to stimulate inflammatory processes and are called pro-inflammatory cytokines.

These changes were mirrored by the cells taken from the subcutaneous and omental fat in vitamin B12-deficient pregnant women. These cells also showed significant changes in the passage of fatty acids through them, and beta-oxidation induced by the supply of palmitate was reduced in the absence of this vitamin.

As a result of these multiple changes, such as increased triglyceride synthesis and reduced fat usage, fat accumulates in the body. Meanwhile the inflammation that was triggered by abnormal fat metabolites also led to disruption of normal body processes. Researcher Jinous Samavat says, “All of [these] predispose to weight gain.”

Implications

Larger numbers of pregnant women must be studied to validate this conclusion. Also, researchers need to find out how the vitamin is important in fat cell workings, so that they can help prevent further ill health and come up with effective intervention techniques. The current team wants to go on to studying how genes are involved in the metabolism of fat cells, and how vitamin B12 deficiency during pregnancy is related to the occurrence of metabolic disease in the offspring over the long term.

Samavat sums it up: "Our findings reinforce the need for Vitamin B12 supplementation during pregnancy and make a strong case for funding further studies and introducing public health policies, to help tackle obesity.”

Journal reference:

Jinous Samavat, Antonysunil Adaikalakoteswari, Joseph Boachie, Laura Jackisch, Philip McTernan, Mark Christian & Ponnusamy Saravanan, Vitamin B12 deficiency leads to fatty acid metabolism dysregulation and increased pro-inflammatory cytokine production in human adipocytes and in maternal subcutaneous and omental adipose tissue, Endocrine Abstracts (2019) 65 P184 | DOI: 10.1530/endoabs.65.P184, https://www.endocrine-abstracts.org/ea/0065/ea0065p184.htm